Search

Pancreatic amyloidosis and loss of α and β cells have been shown to occur in cats with diabetes mellitus, although the number of studies currently available is very limited. Furthermore, it is not known whether pancreatic islet inflammation is a common feature. The aims of the present study were to characterize islet lesions and to investigate whether diabetic cats have inflammation of the pancreatic islets. Samples of pancreas were collected postmortem from 37 diabetic and 20 control cats matched for age, sex, breed, and body weight. Histologic sections were stained with hematoxylin and eosin and Congo red; double labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/proliferating cell nuclear antigen, and glucagon/Ki67; and single labeled for amylin and Iba1. Mean insulin-positive cross-sectional area was approximately 65% lower in diabetic than control cats (P = .009), while that of amylin and glucagon was similar. Surprisingly, amyloid deposition was similar between groups (P = .408). Proliferation of insulin- and glucagon-positive cells and the number of neutrophils, macrophages, and T (CD3) and B (CD20) lymphocytes in the islets did not differ. The presence of T and B lymphocytes combined tended to be more frequent in diabetic cats (n = 8 of 37; 21.6%) than control cats (n = 1 of 20; 5.0%). The results confirm previous observations that loss of β cells but not α cells occurs in diabetic cats. Islet amyloidosis was present in diabetic cats but was not greater than in controls. A subset of diabetic cats had lymphocytic infiltration of the islets, which might be associated with β-cell loss. [ABSTRACT FROM AUTHOR]

In humans, diabetes mellitus (DM) is an important cause of renal damage, with glomerular lesions being predominant. In cats, although diabetes is a common endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of the study was to compare renal histologic features and parameters of renal function in diabetic cats against a control population matched for age, gender, breed, and body weight. Thirty-two diabetic and 20 control cats were included. Kidney sections from paraffin-embedded kidney samples were stained and examined with optical microscopy to identify glomerular, tubulointerstitial, and vascular lesions and to assess their frequency and severity. Serum creatinine and urea concentrations were also compared. Glomerular lesions were observed in 29 cats overall, with mesangial matrix increase being more common (19 cats). Tubulointerstitial lesions were observed in 42 cats, including lymphocytic infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were observed in 5 cases. The frequency and severity of histologic lesions did not differ between diabetic and control cats; however, among diabetics, those that survived longer after diagnosis had more glomerular and vascular lesions. Serum creatinine and urea concentrations were similar between groups; in diabetic cats median creatinine was 109 μmol/l (range, 51–1200) and urea was 12 mmol/l (range, 4–63), and in controls creatinine was 126 μmol/l (range, 50–875) and urea 11 mmol/l (range, 3–80). The results suggest that DM in cats does not lead to microscopically detectable kidney lesions or clinically relevant renal dysfunction. The authors hypothesize that the short life expectancy of diabetic cats may be the main reason for the difference from human diabetics. [ABSTRACT FROM PUBLISHER]

Incretin analogues and inhibitors of the breakdown of endogenous incretins are antidiabetic drugs that increase ß-cell proliferation and glucose-stimulated insulin secretion in rodents and humans. Objectives were to test whether exenatide, exenatide extended-release, and sitagliptin can be safely used in cats, to identify the most effective drug, and to test the effects of prolonged exenatide extended-release administration. Three cats each were given exenatide (0.2-2 μg/kg, q12h, subcutaneously, 5 days), exenatide extended-release (40-400 μg/kg, subcutaneously, once), and sitagliptin (1-10 mg/kg, q24h, orally, 5 days). Before and after treatment, glucose, insulin and glucagon areas under the curve (AUC) were assessed by meal response tests (MRT). Exenatide increased insulin AUC by 224%, 258%, 331% and 93%, exenatide extended-release by 127%, 169%, 178% and 95%, and sitagliptin by 32%, 69%, 62%, and 43%, respectively. The tested drugs are safe to use in cats and enhance insulin secretion. Incretin-based therapy may be beneficial in cats with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: External tags, such as transmitters and loggers, are often used to study bat movements. However, physiological and behavioural effects on bats carrying tags have rarely been investigated, and recommendations on the maximum acceptable tag mass are rather based on rules of thumb than on rigorous scientific assessment., Methods: We conducted a comprehensive three-step assessment of the potential physiological and behavioural effects of tagging bats, using common noctules Nyctalus noctula as a model. First, we examined seasonal changes in body mass. Second, we predicted and then measured potential changes in flight metabolic rate in a wind tunnel. Third, we conducted a meta-analysis of published data to assess effects of different tag masses on the weight and behaviour of bats., Results: Individual body mass of common noctules varied seasonally by 7.0 ± 2.6 g (range: 0.5-11.5 g). Aerodynamic theory predicted a 26% increase in flight metabolic rate for a common noctule equipped with a 3.8 g tag, equating to 14% of body mass. In a wind tunnel experiment, we could not confirm the predicted increase for tagged bats. Our meta-analysis revealed a weak correlation between tag mass and emergence time and flight duration in wild bats. Interestingly, relative tag mass (3-19% of bat body mass) was not related to body mass loss, but bats lost more body mass the longer tags were attached. Notably, relatively heavy bats lost more mass than conspecifics with a more average body mass index., Conclusion: Because heavy tags (> 3 g) were generally used for shorter periods of time than lighter tags (~ 1 g), the long-term effects of heavy tags on bats cannot be assessed at this time. Furthermore, the effects of disturbance and resource distribution in the landscape cannot be separated from those of tagging. We recommend that tags weighing 5-10% of a bat's mass should only be applied for a few days. For longer studies, tags weighing less than 5% of a bat's body mass should be used. To avoid adverse effects on bats, researchers should target individuals with average, rather than peak, body mass indices., (© 2024. The Author(s).)

Objectives: To summarize evidence on the impact of oral health on individual and family economic outcomes, describe trends in the literature, and identify areas for additional research to inform public health research and practice., Methods: Searches were conducted within PubMed, CINAHL, EconLit, Cochrane Library, PsycInfo, and Web of Science databases. Article review, selection, abstraction, and reporting processes were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews., Results: Of 2758 unduplicated records identified, 52 met inclusion criteria. Study outcomes included indicators of employment/employability (n = 9), earnings/earnings potential (n = 26), parent missed work and family financial impacts of child oral health (n = 19), and financial loss (n = 3). Dental caries-related variables were the most common predictors of poorer economic outcomes. Other oral health problems, such as poorer dental functioning or poorer self-reported oral health status, also were associated with adverse economic outcomes. Significant associations with employment were found among studies that assessed interventions designed to improve oral health. Only one study estimated the impact of oral health on earnings. One-third of studies conducted multivariable analyses, and 14% incorporated race and ethnicity variables., Conclusions: Although existing evidence suggests associations between oral health problems and poorer economic outcomes, there is a substantial need for more rigorous research to better understand the extent of economic impact of oral health problems and which populations are most affected. Additional high-quality research is needed to inform which interventions are most likely to improve oral health, reduce adverse economic impacts, and promote health and economic equity., (© 2024 American Association of Public Health Dentistry.)

Urbanization has significant impacts on wildlife and ecosystems and acts as an environmental filter excluding certain species from local ecological communities. Specifically, it may be challenging for some animals to find enough food in urban environments to achieve a positive energy balance. Because urban environments favor small-sized bats with low energy requirements, we hypothesized that common noctules (Nyctalus noctula) acquire food at a slower rate and rely less on conspecifics to find prey in urban than in rural environments due to a low food abundance and predictable distribution of insects in urban environments. To address this, we estimated prey sizes and measured prey capture rates, foraging efforts, and the presence of conspecifics during hunting of 22 common noctule bats equipped with sensor loggers in an urban and rural environment. Even though common noctule bats hunted similar-sized prey in both environments, urban bats captured prey at a lower rate (mean: 2.4 vs. 6.3 prey attacks/min), and a lower total amount of prey (mean: 179 vs. 377 prey attacks/foraging bout) than conspecifics from rural environments. Consequently, the energy expended to capture prey was higher for common noctules in urban than in rural environments. In line with our prediction, urban bats relied less on group hunting, likely because group hunting was unnecessary in an environment where the spatial distribution of prey insects is predictable, for example, in parks or around floodlights. While acknowledging the limitations of a small sample size and low number of spatial replicates, our study suggests that scarce food resources may make urban habitats unfavorable for large bat species with higher energy requirements compared to smaller bat species. In conclusion, a lower food intake may displace larger species from urban areas making habitats with high insect biomass production key for protecting large bat species in urban environments., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Many countries are investing heavily in wind power generation, 1 triggering a high demand for suitable land. As a result, wind energy facilities are increasingly being installed in forests, 2 , 3 despite the fact that forests are crucial for the protection of terrestrial biodiversity. 4 This green-green dilemma is particularly evident for bats, as most species at risk of colliding with wind turbines roost in trees. 2 With some of these species reported to be declining, 5 , 6 , 7 , 8 we see an urgent need to understand how bats respond to wind turbines in forested areas, especially in Europe where all bat species are legally protected. We used miniaturized global positioning system (GPS) units to study how European common noctule bats (Nyctalus noctula), a species that is highly vulnerable at turbines, 9 respond to wind turbines in forests. Data from 60 tagged common noctules yielded a total of 8,129 positions, of which 2.3% were recorded at distances <100 m from the nearest turbine. Bats were particularly active at turbines <500 m near roosts, which may require such turbines to be shut down more frequently at times of high bat activity to reduce collision risk. Beyond roosts, bats avoided turbines over several kilometers, supporting earlier findings on habitat loss for forest-associated bats. 10 This habitat loss should be compensated by developing parts of the forest as refugia for bats. Our study highlights that it can be particularly challenging to generate wind energy in forested areas in an ecologically sustainable manner with minimal impact on forests and the wildlife that inhabit them., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Obesity leads to insulin resistance and is a major risk factor for the development of diabetes mellitus in cats. Prevention of obesity and obesity-induced insulin resistance is difficult, and reliable long-term strategies are currently lacking. Retinoid-related orphan receptor gamma (RORγ) was recently identified as an important transcription factor in the development of large insulin-resistant adipocytes in mice and humans. RORγ negatively affects adipocyte differentiation through expression of its target gene matrix metalloproteinase 3 (MMP3) and promotes the development of large insulin-resistant adipocytes. Preliminary studies in mice showed that RORγ can be inhibited by its ligand tetra-hydroxylated bile acid (THBA). In the present study, serum THBA levels were determined in healthy and diabetic cats. Moreover, potential side effects and the effects of THBA supplementation on adipocyte size, mRNA expression of RORγ, MMP3, interleukin 6, tumor necrosis factor α, adiponectin and leptin in feline subcutaneous adipocytes and insulin sensitivity were investigated in healthy normal weight cats. Thirteen healthy and 13 diabetic cats were used for determination of serum THBA level, and six healthy normal-weight cats were included in a feeding trial. Similar THBA levels were determined in serum of healthy and diabetic cats. Supplementation of 5 mg/kg THBA for 8 wk did not cause any negative effect on feeding behavior, general condition and blood parameters of tested cats. It significantly reduced adipocyte size and mRNA expression of MMP3, interleukin 6, and tumor necrosis factor α in adipocytes, while mRNA expression of adiponectin significantly increased and mRNA expression of RORγ and leptin remained unchanged. Administration of THBA did not influence fasting blood glucose levels or the response of cats to acute insulin administration. Based on these results, THBA is palatable and is considered safe for use in cats. It reduces expression of MMP3 and promotes the development of small adipocytes with increased expression of adiponectin and reduced expression of interleukin 6 and tumor necrosis factor α. Further studies are recommended to evaluate the effect of THBA on adipocyte size and insulin sensitivity in obese cats., (Copyright © 2022. Published by Elsevier Inc.)

Wind energy production is particularly rewarding along coastlines, yet coastlines are often important as migratory corridors for wildlife. This creates a conflict between energy production from renewable sources and conservation goals, which needs to be considered during environmental planning. To shed light on the spatial interactions of a high collision risk bat species with coastal wind turbines (WT), we analysed 32 tracks of 11 common noctule bats (Nyctalus noctula) in Northern Germany with miniaturized global positioning system units yielding 6266 locations. We used three spatial models to infer on the preferred and avoided landscape features in interaction with WT. We found 3.4% of all locations close to WT, with bats preferring areas with high levels of impervious surface, identified as farmhouses. Common noctule bats were also more present close to WT adjacent to paths and waterbodies. At the local scale, >70% of common noctule bats avoided WT, yet if bats approached WT we counted more positions at large WT, specifically close to known roosts. Our study highlights that coastal WT should not be placed next to feeding grounds and bat roosts. Additionally, avoidance of WT by bats indicates that foraging bats may suffer from habitat loss in coastal landscapes with high turbine densities. To mitigate the conflict between wind energy power production and conservation goals at coastal sites, wind turbines should be placed at distance to habitat features preferred by bats and turbine densities should be limited., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hibernation allows species to conserve energy and thereby bridge unfavorable environmental conditions. At the same time, hibernation imposes substantial ecological and physiological costs. Understanding how hibernation timing differs within and between species can provide insights into the underlying drivers of this trade-off. However, this requires individualized long-term data that are often unavailable. Here, we used automatic monitoring techniques and a reproducible analysis pipeline to assess the individualized hibernation phenology of two sympatric bat species. Our study is based on data of more than 1100 RFID-tagged Daubenton's bats (Myotis daubentonii) and Natterer's bats (Myotis nattereri) collected over seven years at a hibernaculum in Germany. We used linear mixed models to analyze species-, sex- and age-specific differences in entrance, emergence and duration of the longest continuous period spent in the hibernaculum., Results: Overall, Daubenton's bats entered the hibernaculum earlier and emerged later than Natterer's bats, resulting in a nearly twice as long hibernation duration. In both species, adult females entered earlier and emerged from hibernation later than adult males. Hibernation duration was shorter for juveniles than adults with the exception of adult male Natterer's bats whose hibernation duration was shortest of all classes. Finally, hibernation timing differed among years, but yearly variations in entrance and emergence timing were not equally shifted in both species., Conclusions: Our results suggest that even in sympatric species, and across sex and age classes, hibernation timing may be differentially affected by environmental conditions. This highlights the necessity of using individualized information when studying the impact of changing environments on hibernation phenology., (© 2022. The Author(s).)

Central nervous system-penetrant therapies with intracranial efficacy against non-small cell lung cancer (NSCLC) brain metastases are urgently needed. We report preclinical studies investigating brain penetration and intracranial activity of the MET inhibitor tepotinib. After intravenous infusion of tepotinib in Wistar rats (n = 3), mean (±standard deviation) total tepotinib concentration was 2.87-fold higher in brain (505 ± 22 ng/g) than plasma (177 ± 20 ng/mL). In equilibrium dialysis experiments performed in triplicate, mean tepotinib unbound fraction was 0.35% at 0.3 and 3.0 µM tepotinib in rat brain tissue, and 4.0% at 0.3 and 1.0 µM tepotinib in rat plasma. The calculated unbound brain-to-plasma ratio was 0.25, indicating brain penetration sufficient for intracranial target inhibition. Of 20 screened subcutaneous patient-derived xenograft (PDX) models from lung cancer brain metastases (n = 1), two NSCLC brain metastases models (LU5349 and LU5406) were sensitive to the suboptimal dose of tepotinib of 30 mg/kg/qd (tumor volume change [%TV]: -12% and -88%, respectively). Molecular profiling (nCounter®; NanoString) revealed high-level MET amplification in both tumors (mean MET gene copy number: 11.2 and 24.2, respectively). Tepotinib sensitivity was confirmed for both subcutaneous models at a clinically relevant dose (125 mg/kg/qd; n = 5). LU5349 and LU5406 were orthotopically implanted into brains of mice and monitored by magnetic resonance imaging (MRI). Tepotinib 125 mg/kg/qd induced pronounced tumor regression, including complete or near-complete regressions, compared with vehicle in both orthotopic models (n = 10; median %TV: LU5349, -84%; LU5406, -63%). Intracranial antitumor activity of tepotinib did not appear to correlate with blood-brain barrier leakiness assessed in T1-weighted gadolinium contrast-enhanced MRI., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Salivary cortisol collected at home is a useful test to diagnose and monitor Cushing's syndrome in humans. The main problem in dogs is to retrieve a sufficient amount of saliva. The aim of this study was to evaluate different salivary collection methods and compare their effects on volume, pH and cortisol concentration of saliva. Sixteen healthy Beagles were used in a 4 × 4 randomized crossover study with a washout period of 1 week between each of the following collection methods: 1. Salimetrics® cotton swab dipped in ginger powder (ginger group); 2. beef-flavored Salimetrics® (bouillon group); 3. Salivette® cotton swab with an enclosed treat (treat group); 4. plain Salimetrics® (control group). First, baseline saliva (plain cotton swab, S0) and, 2 min later, experimental saliva (according to group allocation above, SExp) were collected. Saliva was gathered by holding the swabs in the animal's mouth for 2 min. After the cross-over study, another saliva sample was collected from all dogs by the ginger method, using a 30 s sampling time (30s-ginger method). Cortisol concentrations were measured by liquid chromatography tandem mass spectrometry., Results: All three stimulation methods increased saliva production significantly (S0 compared to SExp: ginger p = 0.0005; bouillon p = 0.009; treat p = 0.007). Only ginger stimulation, however, generated a significantly higher amount of saliva (SExp) compared to the control group (p = 0.00001; median (range) amount of saliva for SExp: ginger 1200 ul (600-1700), bouillon 650 ul (200-1900), treat 700 ul (300-1000), control 400 ul (0-1100)). The amount of saliva retrieved by the 30s-ginger method was still higher than that from the control group (p = 0.0004). Bouillon and treat stimulation led to decreased pH values (bouillon, p = 0.0028; treat, 0.0018). Excitement was higher in the ginger group (p = 0.01). Chewing was intensified in the ginger and treat group (ginger, p = 0.003; treat, 0.0009). The cortisol concentration SExp was higher compared to that of S0 in the ginger and treat group (p = 0.02, 0.003). The experimental cortisol concentrations (SExp) were not different between groups., Conclusions: The 30s-ginger method could prove useful in evaluating or monitoring dogs with Cushing's syndrome, as sampling at home for 30 s by the owner seems feasible.

Background: Decisions about children's oral health care are made by parents. Parents' dental insurance, dental service use, and perceived affordability all influence their children's oral health care., Methods: Using data from the 2016 National Health Interview Survey, the authors constructed a database of 4,396 nationally representative US children and their linked household adults. The authors assessed the relationship between children's and parents' use of dental services, private and public dental insurance, and deferral of oral health care owing to cost. To adjust for factors that may influence outcomes independently, the authors performed multivariate analyses to consider child, parent, and household characteristics., Results: Children have 2 times the risk of lacking a dental visit in a year if the parent has none, 7 times the risk of reportedly lacking dental coverage if the parent has none, and nearly 10 times the risk of having care deferred owing to cost if the parent finds oral health care unaffordable. Affordability risk factors for children include older age and minority race, whereas protective factors include public insurance, parents with higher educational attainment, and female-led households. Increased oral health care use by children was associated with states that provide more extensive adult Medicaid dental benefits., Conclusions: Greater parental dental service use, dental coverage, and ability to afford care benefit their children's use of oral health care., Practice Implications: Policies by employers and government that expand quality private and public coverage for adults hold strong promise to improve oral health care for both parents and their children., (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. Examining treatment-naive or tepotinib-resistant cells with MET amplification or METex14 skipping mutations identifies other receptor tyrosine kinases (RTKs) that co-exist in cells prior to tepotinib exposure and become more prominent upon tepotinib resistance. In a small cohort of patients with lung cancer with MET genetic alterations treated with tepotinib, gene copy number gains of other RTKs were found at baseline and affected treatment outcome. An Src homology 2 domain-containing phosphatase 2 (SHP2) inhibitor delayed the emergence of tepotinib resistance and synergized with tepotinib in treatment-naive and tepotinib-resistant cells as well as in xenograft models. Alternative signaling pathways potentially diminish the effect of tepotinib monotherapy, and the combination of tepotinib with an SHP2 inhibitor enables the control of tumor growth in cells with MET genetic alterations., Competing Interests: L.P., F.J., C.R., C.S., N.L., M.S., D.M., M.K., C.E., A.B., K.M.S., and N.K. are employees of Merck KGaA. A.B. and M.S. hold stocks in Merck KGaA. No other potential conflict of interest relevant to this article was reported., (© 2020 The Author(s).)

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine how income-based disparities in a yearly dental visit (the Healthy People 2020 Leading Health Indicator for Oral Health) changed since legislation to expand dental coverage and to compare disparity trends in children and adults., Methods: We analyzed Medical Expenditure Panel Survey 1997 to 2016 to determine yearly dental visit rates for US children and adults by family income. We determined measures of income disparity, including the Slope Index of Inequality and the Relative Index of Inequality and examined trends in yearly dental visit, Slope Index of Inequality, and Relative Index of Inequality using joinpoint regression., Results: Income-based disparities, absolute and relative, narrowed over time for children. Steady upward trends in yearly dental visit rates were observed for poor and low-income/poor children and no joinpoint was identified that corresponded to legislation expanding dental care coverage for lower income children. Relative income-based disparities in yearly dental visit rates widened for adults over 20 years. After declining for 14 years, yearly dental visit rate increased for poor adults from 2013 to 2016 suggesting a possible positive effect in adult dental care use trends following enactment of the Affordable Care Act., Conclusions: In 1997, US children and adults had similar levels of income-based disparity in yearly dental visits, but by 2016, they differed markedly. Trends in income-based disparities in yearly dental visit rate narrowed for children but widened for adults. There are lessons from the expansion of dental care coverage for children that could be applied to improve access to dental care for adults., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Dogs with hypercortisolism are predisposed to developing bacteriuria associated either with clinical signs of cystitis or without clinical signs (subclinical bacteriuria). Based on current guidelines, dogs with subclinical bacteriuria should not be treated with antibiotics because there is no evidence that treatment improves outcome and because unnecessary treatments should be avoided. Before these guidelines were published in 2019, dogs with hypercortisolism and bacteriuria were commonly treated with antibiotics irrespective of clinical signs. Comprehensive data on the frequency of bacterial cystitis, subclinical bacteriuria and the outcome of antimicrobial treatment in dogs with hypercortisolism is sparse. The aims of this study were to investigate dogs with hypercortisolism for the presence of bacterial cystitis and subclinical bacteriuria, to address the pathogens involved, and to assess the outcome of antibiotic treatment. Dogs newly diagnosed with hypercortisolism between 2005 and 2015 from which a urine bacterial culture was available were included. Statistical analysis was performed with non-parametric tests. Of the 161 client-owned dogs included, 29 (18%) showed bacteriuria, which was subclinical in 24 (83%) cases. Escherichia coli was the most commonly isolated pathogen (58%). Bacteriuria was not associated with sex or neutering status. In 14 dogs, follow-up data was available, of which 13 (93%) were treated with antimicrobials for 14 to 28 days. Follow-up bacterial culture (1 to 118 days after cessation of therapy) was negative in 10 (77%) treated dogs; a negative follow-up culture was not associated with gender, age or duration of treatment. Bacteriuria persisted in three treated dogs and the one untreated dog. The prevalence of positive bacterial urinary culture in dogs with hypercortisolism was lower than previously reported. In the majority of dogs, bacteriuria was subclinical. Most dogs had a negative bacterial culture result after antimicrobial treatment; however, more resistant bacteria were detected in persistently positive urine.

Animals have evolved different cognitive processes to localize crucial resources that are difficult to find. Relevant cognitive processes such as associative learning and spatial memory have commonly been studied in a foraging related context under controlled laboratory conditions. However, in natural environments, animals can use multiple cognitive processes to localize resources. In this field study, we used a pairwise choice experiment and automatic roost monitoring to assess how individually marked, free-ranging Bechstein's bats belonging to two different colonies use associative learning, spatial memory and social information when localizing suitable day roosts. To our knowledge, this study tests for the first time how associative learning, spatial memory and social information are used in the process of roost localization in bats under the natural conditions. We show that, when searching for new roosts, bats used associative learning to discriminate between suitable and unsuitable roosts. For re-localizing previously occupied roosts, bats used spatial memory rather than associative learning. Moreover, bats significantly improved the localization of suitable unfamiliar roosts and tended to increase their accuracy to re-localize previously occupied day roosts using social information. Our field experiments suggest that Bechstein's bats make hierarchical use of different cognitive processes when localizing day roosts. More generally, our study underlines that evaluating different cues under natural conditions is fundamental to understanding how natural selection has shaped the cognitive processes used for localizing resources.

Long-lived animals with a low annual reproductive output need a long time to recover from population crashes and are, thus, likely to face high extinction risk, if the current global environmental change will increase mortality rates. To aid conservation of those species, knowledge on the variability of mortality rates is essential. Unfortunately, however, individual-based multiyear data sets that are required for that have only rarely been collected for free-ranging long-lived mammals. Here, we used a five-year data set comprising activity data of 1,445 RFID-tagged individuals of two long-lived temperate zone bat species, Natterer's bats ( Myotis nattereri ) and Daubenton's bats ( Myotis daubentonii ), at their joint hibernaculum. Both species are listed as being of high conservation interest by the European Habitats Directive. Applying mixed-effects logistic regression, we explored seasonal survival differences in these two species which differ in foraging strategy and phenology. In both species, survival over the first winter of an individual's life was much lower than survival over subsequent winters. Focussing on adults only, seasonal survival patterns were largely consistent with higher winter and lower summer survival but varied in its level across years in both species. Our analyses, furthermore, highlight the importance of species-specific time periods for survival. Daubenton's bats showed a much stronger difference in survival between the two seasons than Natterer's bats. In one exceptional winter, the population of Natterer's bats crashed, while the survival of Daubenton's bats declined only moderately. While our results confirm the general seasonal survival pattern typical for hibernating mammals with higher winter than summer survival, they also show that this pattern can be reversed under particular conditions. Overall, our study points toward a high importance of specific time periods for population dynamics and suggests species-, population-, and age class-specific responses to global climate change., Competing Interests: We have no competing interest.

Introduction: Acromegaly due to a pituitary tumor has so far only been described in 3 dogs. The present case report describes a 7-year-old male-castrated Labrador Retriever which was referred because of difficult-to-control diabetes. Physical examination revealed markedly enlarged head, tongue and paws, widened interdental spaces and thickening of the skin in the head and neck area. IGF-1 and GH were increased and the latter continued to be abnormal after somatostatin application. Computed tomography demonstrated a space-occupying lesion in the pituitary gland and the diagnosis of acromegaly due to a GH-producing tumor of the pituitary was made. The dog underwent radiation therapy with a 6MV linear accelerator (3×8Gy) and improved substantially. Two and a half years after radiation therapy the dog developed lethargy and anorexia and was euthanized. Necropsy was not permitted. This case report represents the description of a dog suffering from pituitary-dependent acromegaly which was successfully treated and had a long-term survival.

Background: The ideal method for monitoring trilostane therapy in dogs with hypercortisolism is still open to debate. Recently, determination of the pre-trilostane (prepill) cortisol concentration has been proposed to be more repeatable than either post-trilostane or post-ACTH cortisol. The aim of this study was to compare two prepill cortisol concentrations in dogs with hypercortisolism during trilostane therapy. Sixteen client-owned dogs with naturally occurring hypercortisolism were prospectively included and cortisol concentrations were measured twice, 1 h apart, before the morning trilostane dose (prepill 1 and 2 cortisol)., Results: A total of 47 prepill cortisol measurement pairs were included. Compared to prepill 1, prepill 2 cortisol was higher in 15, equal in 8 and lower in 24 pairs. Group agreement between prepill 1 and 2 cortisol was 70% (moderate agreement - weighted kappa 0.55). In 30% of the pairs, group assignment was discrepant, implying a different therapeutic decision. In some dogs certain circumstances (e.g. excessive barking, difficulties during blood collection, excitement at arrival) were identified as potential factors explaining the discrepancy between prepill 1 and 2 cortisol measurements., Conclusions: In a substantial number of dogs treated with trilostane, the two prepill cortisol concentrations differed. Part of this difference might be ascribable to stressful events during test performance. When using prepill cortisol measurements to monitor trilostane therapy, recording of any incident during handling that might affect cortisol release might be helpful to make a reliable decision about a trilostane dose adaptation.

Diabetes mellitus is a common endocrinopathy in cats that is associated with pancreatic islets lesions. Research on isolated islets contributed to the understanding of the pathophysiology of human diabetes. Therefore, by improving the existing methods of isolation in cats, we aimed at increasing islet yield, purity and viability of feline isolated islets. Islet isolation was accomplished by pancreas perfusion with 80ml of Collagenase type IV through the pancreatic duct at the site of the major papilla. The enzymatic digestion was combined with mechanical disruption and controlled by dithizone staining. Purification was performed by filtration and handpicking. Purified islets were plated on extracellular matrix pre-coated plates and cultured for 48h. Feline islets with a high degree of viability and purity were isolated and cultured for the first time. Although the percentage of islet free from the acinar tissue relative to the total number of isolated islets was low compared to other species, the suggested protocol represents a promising progress in the procedure of islet isolation in cats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA., Objective: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism., Animals: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled., Methods: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA., Results: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation., Conclusions and Clinical Relevance: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Effects and duration of commonly used protocols for cobalamin (Cbl) supplementation on cellular Cbl deficiency have not been determined in hypocobalaminemic cats., Hypothesis/objectives: To evaluate effect of Cbl supplementation on clinical signs, serum and urine methylmalonic acid (MMA) concentrations over 16 weeks., Animals: Twenty client-owned hypocobalaminemic cats with enteropathy., Methods: Prospective study. Serum Cbl and serum and urine MMA concentrations were determined prospectively in cats at enrollment (t0), immediately before (t6), and 4 (t10) and 10 weeks (t16) after 6th Cbl injection (250 μg, IM q 7 days). Clinical signs severity (activity, appetite, vomiting, diarrhea, body weight) graded at each time point and expressed as clinical disease activity score., Results: Clinical disease activity score decreased during supplementation and increased after treatment discontinuation. Median serum Cbl concentration increased significantly from t0 (111 pmol/L, range 111-212) to t6 (2,332.5 pmol/L, range 123-22,730) (P < 0.01). Values at t10 were 610.5 pmol/L (range, 111-2,527) and 180.5 pmol/L (range, 111-2,262) at t16 (P < 0.01). Median baseline serum MMA concentration (372 μmol/L, range 0.39-147,000) decreased significantly to 1.62 μmol/L (range, 0.18-806) at t6 (P < 0.01) and gradually increased to 5.34 μmol/L (range, 0.13-1,730) at t10 and 189 μmol/L (range, 0.4-983) at t16. Similar, nonsignificant, pattern observed for urine MMA concentration. Serum and urine MMA concentrations had not normalized in 12 and 6 cats, respectively, at t6., Conclusion and Clinical Importance: The Cbl supplementation protocol used here did not lead to complete normalization of cellular Cbl deficiency in all examined cats, and biochemical improvements were transient., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. It is currently believed that different levels of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the identification of new regulators of MEK1/ERK1/2 signalling could help to decipher the context-specific aspects driving the effects of this pathway on SC plasticity. In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity. We depleted KIAA1199 in the SC-derived MSC80 cell line with RNA-interference-based strategy and also generated Tamoxifen-inducible and conditional mouse models in which KIAA1199 is inactivated through homologous recombination, using the Cre-lox technology. We show that the invalidation of KIAA1199 in SC decreases the expression of cJun and other negative regulators of myelination and elevates Krox20, driving them towards a pro-myelinating phenotype. We further show that in dedifferentiation conditions, SC invalidated for KIAA1199 exhibit lower myelin clearance as well as increased myelination capacity. Finally, the Nrg1-induced activation of the MEK/ERK/1/2 pathway is severely reduced when KIAA1199 is absent, indicating that KIAA1199 promotes Nrg1-dependent MEK1 and ERK1/2 activation in SCs. In conclusion, this work identifies KIAA1199 as a novel regulator of MEK/ERK-induced SC dedifferentiation and contributes to a better understanding of the molecular control of SC dedifferentiation., (© 2017 Wiley Periodicals, Inc.)

Background: Glucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy. Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration., Results: Untreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy., Conclusion: Influences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.

The aim of this study was to examine the safety and reliability of a research-grade implantable pump for controlled delivery of insulin glargine in cats. For this purpose, a small telemetrically controlled drug delivery pump with a refillable reservoir was implanted into the subcutaneous tissues of the dorsal neck in 10 clinically healthy cats. The reservoir was filled with insulin glargine, and the pump was programmed to deliver four boluses of 0.25 IU/kg, 2-3 weeks apart. As a control, insulin glargine (0.25 IU/kg) was injected SC. Blood glucose and plasma insulin glargine concentrations were measured before each bolus and SC injection and for 8 h afterward. Cats were monitored for signs of discomfort. Pumps were easily implanted and well tolerated by all cats. The experiment was completed in five of 10 cats. In four, the pump failed because of technical reasons; another cat developed severe hypoglycaemia attributable to insulin leakage. Overall, plasma insulin glargine increased after six of eight (75%) initial boluses and after one of 16 (6%) successive boluses. Glucose decreased after seven of eight (88%) initial boluses and after four of 16 (25%) successive boluses. Only the first bolus significantly increased plasma insulin glargine (P = 0.008) and decreased glucose (P = 0.008). Of 20 SC injections, 10 (50%) increased plasma insulin glargine (P <0.001) and 12 (60%) decreased glucose (P <0.001). The pump did not cause discomfort in cats, but life-threatening hypoglycaemia occurred in one. Frequent device problems suggest that the pump needs improvements. Because successive boluses did not increase plasma insulin glargine, this type of insulin may not be appropriate with the pump., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Trilostane therapy, the treatment of choice for pituitary- dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

Background: Feline pancreas-specific lipase (Spec fPL) is considered a useful test for the antemortem diagnosis of pancreatitis in cats. A recent study found good agreement between the results of the Spec fPL and catalytic 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay. Prospective studies evaluating their sensitivity and specificity are lacking., Objectives: To compare the results of the Spec fPL and the DGGR assays with a standardized histologic assessment of the pancreas., Animals: Sixty client-owned cats presented for necropsy., Prospective Study: Spec fPL concentrations and serum DGGR lipase activity were measured from the same blood sample. The pancreas was removed within 3 hours after euthanasia; serial transverse sections were made every 0.5 cm throughout the entire pancreas and reviewed using a histologic grading scheme. Sensitivity and specificity for the Spec fPL and DGGR assay results were determined., Results: The sensitivity and specificity for the Spec fPL assay (cutoff value ≥5.4 μg/L) was 42.1 [95% confidence interval (95% CI), 29.4-55.9%] and 100% (95% CI, 31.0-100.0%). The sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 36.8 (95% CI, 24.7-50.7%) and 100% (95% CI, 31.0-100.0%). When lymphocytic inflammation up to 10% of a section was considered normal, the sensitivity and specificity for Spec fPL assay (cutoff value ≥5.4 μg/L) was 61.1 (95% CI, 36.1-81.7%) and 69.0% (95% CI, 52.8-81.9%) and the sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 66.7 (95% CI, 41.2-85.6%) and 78.6% (95% CI, 62.8-89.2%)., Conclusions and Clinical Importance: Both lipase assays performed similarly well, but their agreement with histologic pancreatic inflammation was limited., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats., Objectives: The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet., Animals: Thirty client-owned cats., Methods: Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis., Results: Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively)., Conclusion and Clinical Importance: Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: The ACTH stimulation test is used to evaluate the adrenocortical reserve. Recently, the availability of the synthetic ACTH formulation was limited, causing major problems in clinical practice., Objectives: The objective of this study was to evaluate poststimulation peak cortisol concentrations and the duration of the stimulatory effect of a depot ACTH preparation in dogs., Animals: Twenty-two healthy dogs, 10 dogs with suspected hypoadrenocorticism (HA) and 15 dogs with suspected hyperadrenocorticism (HC)., Methods: Prospective study. An ACTH stimulation test using a synthetic depot tetracosactide, administered intramuscularly (5 μg/kg or at least 0.1 mL) was performed. Blood samples for determination of cortisol were taken immediately before and 1, 2, 3, 4, 6, and 24 hours after stimulation., Results: Peak cortisol concentrations were reached after 2-4 hours in all dogs. Cortisol concentrations 1 hour after stimulation were >9 μg/dL in all healthy dogs and >5 μg/dL in all dogs in which HA was excluded. None of the dogs with HA showed a cortisol-increase above the detection-limit of the assay. After 6 hours, cortisol concentrations had decreased in the healthy and HC group and were back to baseline after 24 hours., Conclusions and Clinical Importance: The depot formulation can be used in place of the short-acting ACTH to evaluate the adrenocortical reserve. Blood for peak cortisol concentrations should be drawn 3 hours after stimulation in cases in which HC is suspected; in HA-suspected cases, blood sampling can take place after 1 hour. As the stimulatory effect is gone after 24 hours, interference with other hormonal tests is unlikely after that time., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: The adrenocorticotropic hormone (ACTH) stimulation test is the gold standard for diagnosing hypoadrenocorticism (HA) in dogs. However, problems with the availability of synthetic ACTH (tetracosactrin/cosyntropin) and increased costs have prompted the need for alternative methods., Objectives: To prospectively evaluate the cortisol-to-ACTH ratio (CAR) as a screening test for diagnosing canine HA., Animals: Twenty three dogs with newly diagnosed HA; 79 dogs with diseases mimicking HA; 30 healthy dogs., Methods: Plasma ACTH and baseline cortisol concentrations were measured before i.v. administration of 5 μg/kg ACTH in all dogs. CAR was calculated and the diagnostic performance of ACTH, baseline cortisol, CAR and sodium-to-potassium ratios (SPRs) was assessed based on receiver operating characteristics (ROC) curves calculating the area under the ROC curve., Results: The CAR was significantly lower in dogs with HA compared to that in healthy dogs and in those with diseases mimicking HA (P < .0001). There was an overlap between HA dogs and those with HA mimicking diseases, but CAR still was the best parameter for diagnosing HA (ROC AUC 0.998), followed by the ACTH concentration (ROC AUC 0.97), baseline cortisol concentration (ROC AUC 0.96), and SPR (ROC AUC 0.86). With a CAR of >0.01 the diagnostic sensitivity and specificity were 100% and 99%, respectively., Conclusion and Clinical Importance: Calculation of the CAR is a useful screening test for diagnosing primary HA. As a consequence of the observed overlap between the groups, however, misdiagnosis cannot be completely excluded. Moreover, additional studies are needed to evaluate the diagnostic reliability of CAR in more dogs with secondary HA., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats., Objectives: To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole., Animals: Eight domestic shorthair cats., Methods: Using a randomized 4-way cross-over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo(™) system, starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA., Results: Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice-daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once-daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice-daily omeprazole treatment significantly increased intragastric pH, whereas pH after once-daily omeprazole and ranitidine treatments did not differ from that of placebo-treated cats., Conclusion and Clinical Importance: Only twice-daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

Background: Cats with diabetes mellitus can have subclinical pancreatitis but prospective studies to confirm this are lacking. Metabolic control of diabetic cats with pancreatitis is difficult., Hypothesis: Subclinical pancreatitis occurs in diabetic cats at the time diabetes is diagnosed or might develop during the follow-up period, hampering diabetic remission., Animals: Thirty cats with newly diagnosed diabetes without clinical signs of pancreatitis on admission., Methods: Prospective study. On admission and 2 and 6 months later, serum Spec fPL and DGGR-lipase were measured and the pancreas underwent ultrasonographic examination. Pancreatitis was suspected if serum markers were increased or ≥2 ultrasonographic abnormalities were detected. Cats were treated with insulin glargine and diabetic remission was defined as euglycemia ≥4 weeks after discontinuation of insulin. Nonparametric statistical tests were used for analysis., Results: Subclinical pancreatitis at the time of diagnosis was suspected in 33, 50, and 31% of cats based on Spec fPL, DGGR-lipase and ultrasonography, respectively; and in 60% when diagnostic criteria were combined. During the follow-up period, suspected pancreatitis developed in additional 17-30% cats. Only 1 cat had transient clinical signs compatible with pancreatitis. Seventeen of the 30 cats (57%) achieved remission. Frequency of abnormal Spec fPL and DGGR-lipase and abnormal ultrasonographic findings did not differ in cats achieving remission and those who did not. Cats achieving remission had significantly lower Spec fPL at 2 months (P < .001)., Conclusions and Clinical Importance: Based on laboratory and ultrasonographic measurements, many cats with diabetes might have pancreatitis, although without clinical signs. Cats with high Spec fPL might have a reduced chance of diabetic remission; however, this topic needs further studies in large cohorts of diabetic cats., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine., Objectives: To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC., Animals: Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs., Methods: Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at -80°C before analysis using high-pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration., Results: Dogs with PC had significantly higher urinary normetanephrine and metanephrine:creatinine ratios and significantly higher plasma-total and free normetanephrine and plasma-free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma., Conclusion and Clinical Importance: Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: While the song of all songbirds is controlled by the same neural circuit, the hormone dependence of singing behavior varies greatly between species. For this reason, songbirds are ideal organisms to study ultimate and proximate mechanisms of hormone-dependent behavior and neuronal plasticity., Results: We present the high quality assembly and annotation of a female 1.2-Gbp canary genome. Whole genome alignments between the canary and 13 genomes throughout the bird taxa show a much-conserved synteny, whereas at the single-base resolution there are considerable species differences. These differences impact small sequence motifs like transcription factor binding sites such as estrogen response elements and androgen response elements. To relate these species-specific response elements to the hormone-sensitivity of the canary singing behavior, we identify seasonal testosterone-sensitive transcriptomes of major song-related brain regions, HVC and RA, and find the seasonal gene networks related to neuronal differentiation only in the HVC. Testosterone-sensitive up-regulated gene networks of HVC of singing males concerned neuronal differentiation. Among the testosterone-regulated genes of canary HVC, 20% lack estrogen response elements and 4 to 8% lack androgen response elements in orthologous promoters in the zebra finch., Conclusions: The canary genome sequence and complementary expression analysis reveal intra-regional evolutionary changes in a multi-regional neural circuit controlling seasonal singing behavior and identify gene evolution related to the hormone-sensitivity of this seasonal singing behavior. Such genes that are testosterone- and estrogen-sensitive specifically in the canary and that are involved in rewiring of neurons might be crucial for seasonal re-differentiation of HVC underlying seasonal song patterning.

Information on composition of uroliths collected between 2003 and 2009 from dogs in Switzerland and epidemiologic data of affected dogs are summarised in this paper. Of 490 stones analysed 44% were composed of calcium oxalate, 330% of struvite, 80% of silica, 7% of urate, 3% of cystine, 3% were mixed stones and 1% each were calcium phosphate and xanthine stones. Compared to other dogs, Norwich Terriers, Norfolk Terriers, Miniature Schnauzers, Miniature Pinscher and Yorkshire Terriers had a significantly increased risk to suffer from calcium oxalate stones, Dalmatians and Continental Bulldogs from urate stones and English Bulldogs from cystine stones. No breed had an increased risk of struvite or silica stones. Stones composed of silica were more prevalent in Switzerland compared to other countries and were more common in the eastern part than in the western part of Switzerland. This study shows that there are differences in occurrence and prevalence of uroliths between Switzerland and surveys of other countries.

Background: Remission occurs in 10-50% of cats with diabetes mellitus (DM). It is assumed that intensive treatment improves β-cell function and increases remission rates., Hypothesis: Initial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats., Animals: Thirty cats with newly diagnosed DM., Methods: Prospective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90-180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5-1.0 IU, q12h; >4 kg 1.5-2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis., Results: In groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats (P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats (P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6-month follow-up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013)., Conclusions and Clinical Importance: Initial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)