Y.M. Chang

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age. Hypothesis/Objectives To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension. Animals/Subjects Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified. Methods Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined. Results Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension. Conclusions and Clinical Importance The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.

Genetic analysis of fertility in the Italian Brown Swiss population using different models and trait definitions

The aim of this study was to estimate genetic parameters for fertility and production traits in the Brown Swiss population reared in the Alps (Bolzano-Bozen province, Italy). Fertility indicators were interval from parturition to first service, interval from first service to conception (iFC), and interval from parturition to conception, either expressed as days and as number of potential 21-d estrus cycles (cPF, cFC, and cPC, respectively); number of inseminations to conception; conception rate at first service; and non-return rate at 56 d post-first service. Production traits were peak milk yield, lactation milk yield, lactation length, average lactation protein percentage, and average lactation fat percentage. Data included 71,556 lactations (parities 1 to 9) from 29,582 cows reared in 1,835 herds. Animals calved from 1999 to 2007 and were progeny of 491 artificial insemination bulls. Gibbs sampling and Metropolis algorithms were implemented to obtain (co)variance components using both univariate and bivariate censored threshold and linear sire models. All of the analyses accounted for parity and year-month of calving as fixed effects, and herd, permanent environmental cow, additive genetic sire, and residual as random effects. Heritability estimates for fertility traits ranged from 0.030 (iFC) to 0.071 (cPC). Strong genetic correlations were estimated between interval from parturition to first service and cPF (0.97), and interval from parturition to conception and cPC (0.96). The estimate of heritability for cFC (0.055) was approximately double compared with iFC (0.030), suggesting that measuring the elapsed time between first service and conception in days or potential cycles is not equivalent; this was also confirmed by the genetic correlation between iFC and cFC, which was strong (0.85), but more distant from unity than the other 2 pairs of fertility traits. Genetic correlations between number of inseminations to conception, conception rate at first service, non-return rate at 56 d post-first service, cPF, cFC, and cPC ranged from 0.07 to 0.82 as absolute value. Fertility was unfavorably correlated with production; estimates ranged from -0.26 (cPC with protein percentage) to 0.76 (cPC with lactation length), confirming the genetic antagonism between reproductive efficiency and milk production. Although heritability for fertility is low, the contemporary inclusion of several reproductive traits in a merit index would help to improve performance of dairy cows.

Behavioral and physiological changes around estrus events identified using multiple automated monitoring technologies

This study included 2 objectives. The first objective was to describe estrus-related changes in parameters automatically recorded by the CowManager SensOor (Agis Automatisering, Harmelen, the Netherlands), DVM bolus (DVM Systems LLC, Greeley, CO), HR Tag (SCR Engineers Ltd., Netanya, Israel), IceQube (IceRobotics Ltd., Edinburgh, UK), and Track a Cow (Animart Inc., Beaver Dam, WI). This objective was accomplished using 35 cows in 3 groups between January and June 2013 at the University of Kentucky Coldstream Dairy. We used a modified Ovsynch with G7G protocol to partially synchronize ovulation, ending after the last PGF2α injection (d 0) to allow estrus expression. Visual observation for standing estrus was conducted for four 30-min periods at 0330, 1000, 1430, and 2200h on d 2, 3, 4, and 5. Eighteen of the 35 cows stood to be mounted at least once during the observation period. These cows were used to compare differences between the 6h before and after the first standing event (estrus) and the 2wk preceding that period (nonestrus) for all technology parameters. Differences between estrus and nonestrus were observed for CowManager SensOor minutes feeding per hour, minutes of high ear activity per hour, and minutes ruminating per hour; twice daily DVM bolus reticulorumen temperature; HR Tag neck activity per 2h and minutes ruminating per 2h; IceQube lying bouts per hour, minutes lying per hour, and number of steps per hour; and Track a Cow leg activity per hour and minutes lying per hour. No difference between estrus and nonestrus was observed for CowManager SensOor ear surface temperature per hour. The second objective of this study was to explore the estrus detection potential of machine-learning techniques using automatically collected data. Three machine-learning techniques (random forest, linear discriminant analysis, and neural network) were applied to automatically collected parameter data from the 18 cows observed in standing estrus. Machine learning accuracy for all technologies ranged from 91.0 to 100.0%. When we compared visual observation with progesterone profiles of all 32 cows, we found 65.6% accuracy. Based on these results, machine-learning techniques have potential to be applied to automatically collected technology data for estrus detection.

Clinical Severity Score System in Dogs with Degenerative Mitral Valve Disease

Background Several risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE). Hypothesis/Objectives Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification. Animals Client‐owned dogs (n = 244) with DMVD recruited from first opinion practice. Methods Prospective longitudinal follow‐up of dogs with DMVD. History and PE data were obtained at 6‐month intervals and analyzed with time‐dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken. Results History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes. Conclusions and Clinical Importance Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.

A Comprehensive Pathological Survey of Duodenal Biopsies from Dogs with Diet‐Responsive Chronic Enteropathy

BACKGROUND The detailed pathological phenotype of diet-responsive chronic enteropathy (CE) and its modulation with dietary therapy remain poorly characterized. HYPOTHESIS/OBJECTIVES Key mucosal lesions of diet-responsive CE resolve with dietary therapy. METHODS This was a prospective observational study of 20 dogs with diet-responsive CE. Endoscopic duodenal biopsies collected before and 6 weeks after the start of a dietary trial were assessed by means of qualitative and quantitative histopathological, immunohistochemical, and ultrastructural criteria. Control duodenal biopsies were obtained from 10 healthy Beagle dogs on 1 occasion. RESULTS Compared with control dogs, the CE dogs had higher villus stunting scores and higher overall WSAVA scores, a lower villus height-to-width ratio, and higher lamina propria density of eosinophils. The CE dogs also had ultrastructural lesions of the mitochondria and brush border. In common with other studies in which the disease and control populations are not matched for breed, age, sex, and environment, these comparisons should be interpreted with caution. Comparing biopsies collected at presentation and 6 weeks after starting the dietary trial, mean lamina propria mononuclear cell score and lamina propria densities of eosinophils and mononuclear cells decreased. Dietary therapy also improved ultrastructural lesions of the mitochondria and brush border, eliciting a decrease in intermicrovillar space and an increase in microvillus height. CONCLUSIONS AND CLINICAL IMPORTANCE In dogs with diet-responsive CE, the remission of clinical signs with dietary therapy is associated with subtle decreases in lamina propria density of eosinophils and mononuclear cells, and resolution of ultrastructural lesions of the enterocyte.

A validation of technologies monitoring dairy cow feeding, ruminating, and lying behaviors.

The objective of this study was to evaluate commercially available precision dairy technologies against direct visual observations of feeding, rumination, and lying behaviors. Primiparous (n=24) and multiparous (n=24) lactating Holstein dairy cattle (mean ± standard deviation; 223.4±117.8 d in milk, producing 29.2±8.2kg of milk/d) were fitted with 6 different triaxial accelerometer technologies evaluating cow behaviors at or before freshening. The AfiAct Pedometer Plus (Afimilk, Kibbutz Afikim, Israel) was used to monitor lying time. The CowManager SensOor (Agis, Harmelen, Netherlands) monitored rumination and feeding time. The HOBO Data Logger (HOBO Pendant G Acceleration Data Logger, Onset Computer Corp., Pocasset, MA) monitored lying time. The CowAlert IceQube (IceRobotics Ltd., Edinburgh, Scotland) monitored lying time. The Smartbow (Smartbow GmbH, Jutogasse, Austria) monitored rumination time. The Track A Cow (ENGS, Rosh Pina, Israel) monitored lying time and time spent around feeding areas for the calculation of feeding time. Over 8 d, 6 cows per day were visually observed for feeding, rumination, and lying behaviors for 2 h after morning and evening milking. The time of day was recorded when each behavior began and ended. These times were used to generate the length of time behaviors were visually observed. Pearson correlations (r; calculated using the CORR procedure of SAS Version 9.3, SAS Institute Inc., Cary, NC), and concordance correlations (CCC; calculated using the epiR package of R version 3.1.0, R Foundation for Statistical Computing, Vienna, Austria) evaluated association between visual observations and technology-recorded behaviors. Visually recorded feeding behaviors were moderately correlated with the CowManager SensOor (r=0.88, CCC=0.82) and Track A Cow (r=0.93, CCC=0.79) monitors. Visually recorded rumination behaviors were strongly correlated with the Smartbow (r=0.97, CCC=0.96), and weakly correlated with the CowManager SensOor (r=0.69, CCC=0.59). Visually recorded lying behaviors were strongly correlated with the AfiAct Pedometer Plus (r >0.99, CCC >0.99), CowAlert IceQube (r >0.99, CCC >0.99), and Track A Cow (r >0.99, CCC >0.99). The HOBO Data Loggers were moderately correlated (r >0.83, CCC >0.81) with visual observations. Based on these results, the evaluated precision dairy monitoring technologies accurately monitored dairy cattle behavior.

Machine-learning-based calving prediction from activity, lying, and ruminating behaviors in dairy cattle

The objective of this study was to use automated activity, lying, and rumination monitors to characterize prepartum behavior and predict calving in dairy cattle. Data were collected from 20 primiparous and 33 multiparous Holstein dairy cattle from September 2011 to May 2013 at the University of Kentucky Coldstream Dairy. The HR Tag (SCR Engineers Ltd., Netanya, Israel) automatically collected neck activity and rumination data in 2-h increments. The IceQube (IceRobotics Ltd., South Queensferry, United Kingdom) automatically collected number of steps, lying time, standing time, number of transitions from standing to lying (lying bouts), and total motion, summed in 15-min increments. IceQube data were summed in 2-h increments to match HR Tag data. All behavioral data were collected for 14 d before the predicted calving date. Retrospective data analysis was performed using mixed linear models to examine behavioral changes by day in the 14 d before calving. Bihourly behavioral differences from baseline values over the 14 d before calving were also evaluated using mixed linear models. Changes in daily rumination time, total motion, lying time, and lying bouts occurred in the 14 d before calving. In the bihourly analysis, extreme values for all behaviors occurred in the final 24 h, indicating that the monitored behaviors may be useful in calving prediction. To determine whether technologies were useful at predicting calving, random forest, linear discriminant analysis, and neural network machine-learning techniques were constructed and implemented using R version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). These methods were used on variables from each technology and all combined variables from both technologies. A neural network analysis that combined variables from both technologies at the daily level yielded 100.0% sensitivity and 86.8% specificity. A neural network analysis that combined variables from both technologies in bihourly increments was used to identify 2-h periods in the 8 h before calving with 82.8% sensitivity and 80.4% specificity. Changes in behavior and machine-learning alerts indicate that commercially marketed behavioral monitors may have calving prediction potential.

Neutrophil Gelatinase‐Associated Lipocalin in Dogs With Sepsis Undergoing Emergency Laparotomy: A Prospective Case–Control Study

Background Neutrophil gelatinase‐associated lipocalin (NGAL) is an early indicator of acute kidney injury (AKI) in dogs and its use has not been evaluated in dogs with sepsis. Animals Fifteen dogs with sepsis requiring laparotomy (study dogs) and 10 dogs undergoing surgery for intervertebral disc disease (control dogs). Objective To determine whether NGAL increases in dogs with sepsis undergoing emergency laparotomy and whether it is correlated with development of AKI and survival. Methods Longitudinal study conducted at a referral teaching hospital. Serum neutrophil gelatinase‐associated lipocalin (sNGAL), urinary NGAL normalized to urinary creatinine concentration (UNCR), and serum creatinine concentration were measured at 4 time points (admission, after anesthesia, and 24 and 48 hours postsurgery). Development of AKI (increase in serum creatinine concentration of 0.3 mg/dL) and in‐hospital mortality were recorded. Linear mixed‐model analysis was employed to assess differences between groups over time. Mann–Whitney U‐test was performed for comparison of continuous variables between groups and Chi square or Fishers exact tests were used to assess correlation between discrete data. Results Serum NGAL and UNCR were significantly higher in study dogs across all time points (P = .007 and P < .001, respectively) compared with controls. Urinary NGAL normalized to creatinine in the study group was not significantly different between survivors (n = 12) and nonsurvivors (n = 3). Dogs that received hydroxyethyl starch had significantly higher UNCR across all time points (P = .04) than those that did not. Discussion—Conclusion Serum neutrophil gelatinase‐associated lipocalin and UNCR are increased in dogs with sepsis requiring emergency laparotomy. Additional studies are needed to evaluate its role as a marker of AKI in this population.

Prevalence of FoxP3+ Cells in Canine Tumours and Lymph Nodes Correlates Positively with Glucose Transporter 1 Expression

Hypoxia and regulatory T cells (Tregs) in tumours are both known to be negative prognostic factors in cancer, and this study demonstrated a correlation between the two factors in canine neoplasia. Samples of 57 canine tumours and 29 canine lymph nodes categorized as tumour-draining, with or without metastasis, or reactive and not tumour-associated, were examined. Sequential sections were labelled by immunohistochemistry for glucose transporter 1 (Glut1) and FoxP3 as markers of hypoxia and Tregs, respectively. Up to 21 regions of interest (ROI) were selected in each section in a representative pattern and were assigned a semiquantitative score based on Glut1 labelling. The number of FoxP3(+) cells within each ROI was counted. A generalized estimating equation with negative binomial log link function was used to determine an association between Glut1 expression and FoxP3(+) cell count. Higher Glut1 immunoreactivity was correlated with significantly higher numbers of FoxP3(+) cells in the total tumour sample pool and total lymph node sample pool. Analysis of various subcategories of tumours and lymph nodes showed that this correlation was also present within samples characterized as malignant, haemopoietic mesenchymal tumours, non-haemopoietic mesenchymal tumours, epithelial tumours, lymphoma, lymph nodes containing metastases and reactive lymph nodes. These results indicate that hypoxia in canine tumours may result in an increased infiltration by Tregs.

The Effect of Moderate Dietary Protein and Phosphate Restriction on Calcium-Phosphate Homeostasis in Healthy Older Cats

Background Dietary phosphate and protein restriction decreases plasma PTH and FGF‐23 concentrations and improves survival time in azotemic cats, but has not been examined in cats that are not azotemic. Hypothesis Feeding a moderately protein‐ and phosphate‐restricted diet decreases PTH and FGF‐23 in healthy older cats and thereby slows progression to azotemic CKD. Animals A total of 54 healthy, client‐owned cats (≥ 9 years). Methods Prospective double‐blinded randomized placebo‐controlled trial. Cats were assigned to test diet (protein 76 g/Mcal and phosphate 1.6 g/Mcal) or control diet (protein 86 g/Mcal and phosphate 2.6 g/Mcal) and monitored for 18 months. Changes in variables over time and effect of diet were assessed by linear mixed models. Results A total of 26 cats ate test diet and 28 cats ate control diet. There was a significant effect of diet on urinary fractional excretion of phosphate (P = 0.045), plasma PTH (P = 0.005), and ionized calcium concentrations (P = 0.018), but not plasma phosphate, FGF‐23, or creatinine concentrations. Plasma PTH concentrations did not significantly change in cats fed the test diet (P = 0.62) but increased over time in cats fed the control diet (P = 0.001). There was no significant treatment effect of the test diet on development of azotemic CKD (3 of 26 (12%) test versus 3 of 28 (11%) control, odds ratio 1.09 (95% CI 0.13–8.94), P = 0.92). Conclusions and Clinical Importance Feeding a moderately protein‐ and phosphate‐restricted diet has effects on calcium‐phosphate homeostasis in healthy older cats and is well tolerated. This might have an impact on renal function and could be useful in early chronic kidney disease.