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OBJECTIVE: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10). METHODS: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatographytandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10. RESULTS: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences. CLINICAL RELEVANCE: Some significant metabolite differences were identified between dogs with and without cardiac cachexia. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare signalment, clinical signs, diet, echocardiographic findings, and outcome for pit bull–type breeds diagnosed between 2015 and 2022 with dilated cardiomyopathy (DCM) or with DCM diagnosed by a cardiologist but that did not meet all study echocardiographic criteria (DCM-C). ANIMALS 91 dogs with DCM and 11 dogs with DCM-C. PROCEDURES Data were collected on clinical findings, echocardiographic measurements, and diet at the time of diagnosis (for 76/91 dogs); echocardiographic changes; and survival. RESULTS For dogs with diet information available for time of diagnosis, 64/76 (84%) dogs were eating nontraditional commercial diets, while 12/76 (16%) were eating traditional commercial diets. There were few differences between diet groups at baseline, with congestive heart failure and arrhythmias common in both groups. Thirty-four dogs with known baseline diet and diet change status had follow-up echocardiograms between 60 and 1,076 days later (traditional diet, n = 7; nontraditional diet that changed diets, 27; and nontraditional diet group without diet change, 0). Dogs in the nontraditional diet group that changed diets had a significantly greater decrease in normalized left ventricular diameter (diastolic, P = .02; systolic, P = .048) and the left atrium-to-aorta ratio (P = .002) and a significantly greater increase in fractional shortening (P = .02) compared to dogs eating traditional diets. Dogs eating nontraditional diets with diet change (n = 45; P < .001) and dogs eating traditional diets (12; P < .001) had a significantly longer survival time compared to dogs eating nontraditional diets without diet change (4). Dogs with DCM-C also had significant echocardiographic improvements after diet change. CLINICAL RELEVANCE Congestive heart failure and arrhythmias were common in pit bull–type breeds with DCM. Those eating nontraditional diets that changed diets had significant improvements in echocardiographic measurements after diet change. [ABSTRACT FROM AUTHOR]

Background: Recent studies have investigated dogs with presumed diet‐associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed. Hypothesis/Objectives: To evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD. Animals: Sixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs. Methods: Echocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months). Results: At enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P =.005). Median survival time for dogs with DCM was 611 days (range, 2‐940 days) for the NTD group and 161 days (range, 12‐669 days) for the TD group (P =.21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time. Conclusions and Clinical Importance: Dogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes. [ABSTRACT FROM AUTHOR]

Background: The benefits of pimobendan in the treatment of congestive heart failure (CHF) in cats with hypertrophic cardiomyopathy (HCM) have not been evaluated prospectively. Hypothesis/Objectives: To investigate the effects of pimobendan in cats with HCM and recent CHF and to identify possible endpoints for a pivotal study. We hypothesized that pimobendan would be well‐tolerated and associated with improved outcome. Animals Eighty‐three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction. Methods: Prospective randomized placebo‐controlled double‐blind multicenter nonpivotal field study. Cats received either pimobendan (0.30 mg/kg q12h, n = 43), placebo (n = 39), or no medication (n = 1) together with furosemide (<10 mg/kg/d) with or without clopidogrel. The primary endpoint was a successful outcome (ie, completing the 180‐day study period without a dose escalation of furosemide). Results: The proportion of cats in the full analysis set population with a successful outcome was not different between treatment groups (P =.75). For nonobstructive cats, the success rate was 32% in pimobendan‐treated cats versus 18.2% in the placebo group (odds ratio [OR], 2.12; 95% confidence interval [CI], 0.54‐8.34). For obstructive cats, the success rate was 28.6% and 60% in the pimobendan and placebo groups, respectively (OR, 0.27; 95% CI, 0.06‐1.26). No difference was found between treatments for the secondary endpoints of time to furosemide dose escalation or death (P =.89). Results were similar in the per‐protocol sets. Adverse events in both treatment groups were similar. Conclusions and Clinical Importance: In this study of cats with HCM and recent CHF, no benefit of pimobendan on 180‐day outcome was identified. [ABSTRACT FROM AUTHOR]

Background: Cardiac disease in dogs impacts the quality of life (QoL) of their owners, but owners' QoL has not been comprehensively assessed in this population. Objectives: To develop, validate, and provide preliminary data from a health‐related QoL (hrQoL) questionnaire for owners of dogs with cardiac disease. Subjects: A total of 141 owners of dogs with cardiac disease were studied. Methods: An owner hrQoL (O‐hrQoL) questionnaire containing 20 items related to areas of a person's life that could be impacted by caring for a dog with cardiac disease was developed and administered to owners of dogs with cardiac disease. The highest possible total score was 100, with higher scores indicating a worse hrQoL. Readability, internal consistency, face and construct validity, and item‐total correlations were assessed. Results: Median O‐hrQoL score was 35 (range, 0‐87). The questionnaire had good internal consistency (Cronbach's α = 0.933), construct validity (Spearman's r = 0.38‐0.53; Kendall's τ = 0.30‐0.43; P <.001), and item‐total correlation (Spearman's r = 0.44‐0.79; Kendall's τ = 0.34‐0.66; all P <.001). Fifty percent of owners indicated a negative effect of dogs' cardiac disease on their own QoL, but all owners responded that caring for their dogs either had strengthened (n = 76; 53.9%) or had no effect on their relationship with their dog (n = 65; 46.1%). Conclusions and clinical importance: The O‐hrQoL questionnaire had good validity, and results suggest that owners' QoL is significantly impacted by caring for dogs with cardiac disease. Additional research on effective approaches to minimizing the negative effects of a dog's cardiac disease on the owner is warranted. [ABSTRACT FROM AUTHOR]

Background: Focused cardiac ultrasound (FCU) helps detect occult heart disease in human patients. Hypothesis: Focused cardiac ultrasound by a nonspecialist practitioner (NSP) will increase the detection of occult heart disease in asymptomatic cats compared with physical examination and ECG. Animals: Three hundred forty‐three client‐owned cats: 54 excluded and 289 analyzed. Methods: Multicenter prospective cohort study. Twenty‐two NSPs were trained to perform FCU. Cats without clinical signs of heart disease were recruited, and NSPs performed the following in sequential order: physical examination, ECG, FCU, and point‐of‐care N‐terminal pro‐B‐type natriuretic peptide assay (POC‐BNP). After each step, NSPs indicated yes, no, or equivocal as to whether they believed heart disease was present. The level of agreement between the NSP diagnosis and a blinded cardiologist's diagnosis after echocardiogram was evaluated using Cohen's kappa test. Results: Cardiologist diagnoses included 148 normal cats, 102 with heart disease, and 39 equivocal ones. Agreement between NSP and cardiologist was slight after physical examination (kappa 0.253 [95% CI, 0.172‐0.340]), did not increase after ECG (0.256 [0.161‐0.345]; P =.96), increased after FCU (0.468 [0.376‐0.558]; P =.002), and the level of agreement was similar after POC‐BNP (0.498 [0.419‐0.580]; P =.67). In cats with mild, moderate, and marked occult heart disease, the proportion of cats having a NSP diagnosis of heart disease after FCU was 45.6%, 93.1%, and 100%, respectively. Conclusions and Clinical Importance: Focused cardiac ultrasound performed by NSPs increased the detection of occult heart disease, especially in cats with moderate to marked disease. Focused cardiac ultrasound appears to be a feasible and useful tool to assist NSPs in the detection of heart disease in cats. [ABSTRACT FROM AUTHOR]

Background: Pathophysiologic mechanisms for the development and progression of degenerative mitral valve disease (DMVD) remain elusive. Increased concentrations of circulating trimethylamine N‐oxide (TMAO) and its precursors choline and l‐carnitine are associated with the presence and severity of heart disease in people. Objectives: To determine if differences exist in plasma concentrations of TMAO, choline, or l‐carnitine among dogs with DMVD and congestive heart failure (CHF), dogs with asymptomatic DMVD, and healthy control dogs. Animals Thirty client‐owned dogs: 10 dogs with CHF secondary to DMVD, 10 dogs with asymptomatic DMVD, and 10 healthy control dogs. Methods: A pilot cross‐sectional study in which echocardiography was performed and fasting plasma concentrations of TMAO, choline, and l‐carnitine (total and fractions) were measured. Results: TMAO (P = .03), total l‐carnitine (P = .03), carnitine esters (P = .05), and carnitine esters to free carnitine ratio (E/F ratio; P = .05) were significantly higher in dogs with CHF compared to those with asymptomatic DMVD. TMAO (P = .02), choline (P = .01), total l‐carnitine (P = .01), carnitine esters (P = .02), free carnitine (P = .02), and E/F ratio (P = .009) were significantly higher in dogs with CHF compared to healthy controls. Conclusions and Clinical Importance: Dogs with CHF secondary to DMVD had higher concentrations of TMAO compared to both asymptomatic DMVD dogs and healthy controls. Larger prospective studies are warranted to determine if TMAO plays a role in the development or progression of DMVD or CHF. [ABSTRACT FROM AUTHOR]

In humans, heart disease is associated with high caregiver burden and stress, which can negatively affect the health-related quality of life (hrQoL) of both patient and caregiver. The effect of a dog's heart disease on owners' hrQoL has not been reported. Therefore, the objective of this study was to develop and validate a hrQoL questionnaire for owners of dogs with heart disease, with the hypothesis that heart disease would impact the hrQoL of owners. Owners of dogs with degenerative mitral valve disease, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyo - pathy were eligible for the study. A 7-item questionnaire was developed, with a possible range of scores from 0-35 (higher scores indicated worse owner hrQoL). The questionnaire was self-administered by owners and results were analyzed to determine validity, test-retest reliability, and internal consistency. The Functional EvaluaTion of Cardiac Health (FETCH) questionnaire was used to assess dogs' hrQoL. Two hundred and seventeen owners of dogs with heart disease were enrolled. Median owner hrQoL score was 6 (range, 0-31) and median FETCH hrQoL score was 7 (range, 0-70). The owner hrQoL score was correlated with the FETCH score (r = 0.76, p < 0.001) and severity of dogs' disease (r = 0.53, p < 0.001). Test-retest reliability was high (r = 0.83, p < 0.001). These results suggest that the owner hrQoL questionnaire has good reliability and validity, and that further testing of this questionnaire is warranted to optimize communication with owners regarding the care of dogs with heart disease. [ABSTRACT FROM AUTHOR]

Background: Dogs with advanced heart failure are a clinical challenge for veterinarians but there are no studies reporting clinical features and outcome of this population. Hypothesis/Objectives: To describe clinical findings and outcome of dogs with advanced heart failure caused by degenerative mitral valve disease (DMVD). Animals: Fifty-four dogs with advanced heart failure because of DMVD. Methods: For study purposes, advanced heart failure was defined as recurrence of congestive heart failure signs despite receiving the initially prescribed dose of pimobendan, angiotensin-converting-enzyme inhibitor (ACEI), and furosemide >4 mg/kg/day. Data were collected for the time of diagnosis of Stage C heart failure and time of diagnosis of advanced heart failure. Date of death was recorded. Results: At the diagnosis of advanced heart failure, doses of pimobendan (n530), furosemide (n528), ACEI (n513), and spironolactone (n54) were increased, with ≥1 new medications added in most dogs. After initial diagnosis of advanced heart failure, 38 (70%) dogs had additional medications adjustments (median52 [range, 0-27]), with the final total medication number ranging from 2-10 (median55). Median survival time after diagnosis of advanced heart failure was 281 days (range, 3-885 days). Dogs receiving a furosemide dose >6.70 mg/kg/day had significantly longer median survival times (402 days [range, 3-885 days] versus 129 days [range 9-853 days]; P5.017). Conclusions and Clinical Importance: Dogs with advanced heart failure can have relatively long survival times. Higher furosemide dose and non-hospitalization were associated with longer survival. [ABSTRACT FROM AUTHOR]

Objective To assess abnormalities in concentrations of cardiac troponin I (cTnI ), lactate, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in relation to arrhythmias, echocardiographic measurements, and survival in dogs with gastric dilatation volvulus (GDV). Design Prospective observational study. Setting University hospital. Animals Twenty-two dogs with naturally occurring GDV. Samples Concentrations of cTnI , plasma lactate, and NT-proBNP were recorded at presentation to the emergency room, the time closest to echocardiography, and the highest recorded concentrations during hospitalization. Interventions None. Measurements and Main Results Cardiac rhythms were categorized on a 0-4 scale (0 = no ventricular premature complexes [VPCs], 1 = single VPCs, 2 = bigeminy or trigeminy, 3 = couplets or triplets, and 4 = R-on-T phenomenon or ventricular tachycardia). Echocardiography was performed 6-18 hours postoperatively. Fifteen dogs had ventricular arrhythmias during hospitalization (Grade 1 [ n = 9], Grade 4 [ n = 6]). The highest recorded cTnI concentration was significantly higher in the dogs with Grade 4 ( P = 0.002) or Grade 1 ( P = 0.001) arrhythmias compared to dogs without arrhythmias. Plasma lactate was significantly correlated with left ventricular internal diameter in diastole ( r = −0.52, P = 0.01) and systole ( r = −0.57, P = 0.006), left ventricular free wall in diastole (LWDd, r = 0.59, P = 0.004), and interventricular septal thickness in diastole (IVDs, r = 0.65, P = 0.001). Dogs that did not survive to 1 week postdischarge (3/22) had a significantly thicker LVWd ( P = 0.04) and IVSd ( P = 0.05), and received significantly less fluids in the first 24 ( P = 0.02) and 48 hours ( P = 0.03) of hospitalization. Conclusions Concentrations of cTnI and NT-proBNP increased during hospitalization, but only cTnI concentrations were significantly higher in dogs with a higher arrhythmia grade. Additional research on the potential role of serial measurement of biomarkers in dogs with GDV is warranted. [ABSTRACT FROM AUTHOR]

Large multi-user facilities serve many thousands of researchers in fields from particle physics to fundamental biology. The great expense-up to billions of current-day dollars-and the complexity of such facilities required access to extensive engineering and research infrastructures, most often found at national laboratories and the largest research universities. Although the development of such facilities has been largely successful and the research results unique and often spectacular, the processes for choosing, funding, and locating them were complex and not always productive. In this review, I describe the troubled efforts over the past fifty years to develop neutron research facilities in the United States. During this period, the US has moved from a preeminent position in neutron-based science to a lesser status with respect to Europe. Several major US centers of excellence have been shut down and replaced with more focused capabilities. I compare the US efforts in neutron facilities with parallel developments in Europe and Asia, discuss the reasons for this state of affairs, and make some suggestions to help prevent similar consequences in the future. [ABSTRACT FROM AUTHOR]

Objective To determine whether a training course in focused echocardiography can improve the proficiency of noncardiology house officers in accurately interpreting cardiovascular disease and echocardiography findings in dogs entering the emergency room setting. Design Prospective, blinded, educational study. Setting University veterinary teaching hospital. Study Subjects House officers underwent training in focused echocardiography. Fifteen dogs, including normal dogs and dogs with stable congenital or acquired cardiac disease, were used as study subjects during the laboratory session. Interventions A 6-hour curriculum on focused echocardiography was developed that included didactic lectures, clinical cases, and hands-on echocardiography. Measurements and Main Results Pre- and postcourse written examinations were administered to participants. House officers attended didactic lectures that were subsequently followed by a hands-on laboratory session and practical examination, which involved performing transthoracic echocardiography on dogs with and without cardiovascular disease. Twenty-one house officers completed the focused echocardiography training course. Written examination scores were 57 ± 12% before and 75 ± 10% after training ( P < 0.001). Following the course, 97% of participants in the practical examination were able to obtain the correct right parasternal short- or long-axis view. Posttraining, most participants correctly identified pleural effusion (90%) and pericardial effusion (95%) and discriminated normal atrial size from atrial enlargement (86%). However, successful identification of a cardiac mass, volume status, and ability to recognize a poor quality study as nondiagnostic remained relatively low. Most trainees responded that the length of hands-on laboratory training was too abbreviated and that the course should be > 6 hours. Conclusion A focused echocardiography training course improved knowledge and yielded acceptable proficiency in some echocardiographic findings commonly identified in the emergency room. This training course was not able to provide the skills needed for house officers to accurately assess fluid volume status, identify cardiac masses, ventricular enlargement or hypertrophy, and certain cardiac diseases. [ABSTRACT FROM AUTHOR]

Objective--To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats. Animals--30 healthy cats without evidence of cardiomyopathy on echocardiographic examination. Procedures--All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration. Results--All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different. Conclusions and Clinical Relevance--Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats. [ABSTRACT FROM AUTHOR]

Objective To systematically evaluate the evidence of the effect of advanced life support techniques on outcome in veterinary cardiopulmonary resuscitation (CPR) and to outline knowledge gaps. Design Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical practice. Setting Academia, referral practice, and general practice Results Sixteen population, intervention, control group, outcome questions were evaluated to determine if recommendations could be made concerning drug therapy, including vasopressors, vagolytics, corticosteroids, reversal agents, buffer therapy, and correction of electrolyte disturbances. Electrical defibrillation strategies as well as other advanced interventions such as open-chest CPR, impedance threshold devices, and special considerations regarding anesthesia-related cardiopulmonary arrest (CPA) were also investigated. Conclusions There is strong evidence supporting the use of standard-dose (0.01 mg/kg) epinephrine in CPR, as well as early electrical defibrillation for animals experiencing CPA due to ventricular fibrillation or pulseless ventricular tachycardia, preferentially using a biphasic defibrillator. For CPA due to certain causes and with the availability of advanced postcardiac arrest support, open chest CPR is preferred. Many knowledge gaps regarding other pharmacologic and advanced therapies were identified, and further studies are recommended to better systematically address these questions. [ABSTRACT FROM AUTHOR]

Objective—To develop, validate, and evaluate a questionnaire (Cats' Assessment Tool for Cardiac Health [CATCH] questionnaire) for assessing health-related quality of life in cats with cardiac disease. Design—Prospective study. Animals—275 cats with cardiac disease. Procedures—The questionnaire was developed on the basis of clinical signs of cardiac disease in cats. A CATCH score was calculated by summing responses to questionnaire items; possible scores ranged from 0 to 80. For questionnaire validation, owners of 75 cats were asked to complete the questionnaire (10 owners completed the questionnaire twice). Disease severity was assessed with the International Small Animal Cardiac Health Council (ISACHC) classification for cardiac disease. Following validation, the final questionnaire was administered to owners of the remaining 200 cats. Results—Internal consistency of the questionnaire was good, and the CATCH score was significantly correlated with ISACHC classification. For owners that completed the questionnaire twice, scores were significantly correlated. During the second phase of the study, the CATCH score ranged from 0 to 74 (median, 7) and was significantly correlated with ISACHC classification. Conclusions and Clinical Relevance—Results suggested that the CATCH questionnaire is a valid and reliable method for assessing health-related quality of life in cats with cardiac disease. Further research is warranted to test the tool's sensitivity to changes in medical treatment and its potential role as a clinical and research tool. [ABSTRACT FROM AUTHOR]

Summary: Dynamic reorganization of signaling systems frequently accompanies pathway perturbations, yet quantitative studies of network remodeling by pathway stimuli are lacking. Here, we report the development of a quantitative proteomics platform centered on multiplex absolute quantification (AQUA) technology to elucidate the architecture of the cullin-RING ubiquitin ligase (CRL) network and to evaluate current models of dynamic CRL remodeling. Current models suggest that CRL complexes are controlled by cycles of CRL deneddylation and CAND1 binding. Contrary to expectations, acute CRL inhibition with MLN4924, an inhibitor of the NEDD8-activating enzyme, does not result in a global reorganization of the CRL network. Examination of CRL complex stoichiometry reveals that, independent of cullin neddylation, a large fraction of cullins are assembled with adaptor modules, whereas only a small fraction are associated with CAND1. These studies suggest an alternative model of CRL dynamicity where the abundance of adaptor modules, rather than cycles of neddylation and CAND1 binding, drives CRL network organization. [Copyright &y& Elsevier]

Objective - To determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is useful in discriminating between cardiac and noncardiac (ie, primary respiratory tract disease) causes of respiratory signs (ie, coughing, stertor, stridor, excessive panting, increased respiratory effort, tachypnea, or overt respiratory distress) in dogs. Design - Multicenter cross-sectional study. Animals - 115 dogs with respiratory signs. Procedures - Dogs with respiratory signs were solicited for study. Physical examination, thoracic radiography, and echocardiography were used to determine whether respiratory signs were the result of cardiac (ie, congestive heart failure) or noncardiac (ie, primary respiratory tract disease) causes. Serum samples for NT-proBNP assay were obtained at time of admission for each dog. Receiver-operating characteristic curves were constructed to determine the ability of serum NT-proBNP concentration to discriminate between cardiac and noncardiac causes of respiratory signs. Results - Serum NT-proBNP concentration was significantly higher in dogs with cardiac versus non-cardiac causes of respiratory signs. In dogs with primary respiratory tract disease, serum NT-proBNP concentration was significantly higher in those with concurrent pulmonary hypertension than in those without. A serum NT-proBNP cutoff concentration > 1,158 pmol/L discriminated between dogs with congestive heart failure and dogs with primary respiratory tract disease with a sensitivity of 85.5% and a specificity of 81.3%. Conclusions and Clinical Relevance - Measuring serum NT-proBNP concentration in dogs with respiratory signs helps to differentiate between congestive heart failure and primary respiratory tract disease as an underlying cause. [ABSTRACT FROM AUTHOR]

Objective To determine if cats with congestive heart failure (CHF) are presented to a referral clinic more frequently during different seasons, months, days, or times. Design Retrospective study. Setting University small animal hospital. Animals One hundred and eighty-six cats with CHF. Interventions None. Measurements and Main Results The medical records of 186 cats, presented for 238 episodes of CHF between July 1, 1997 and June 30, 2002, were reviewed. An episode of CHF was defined as documented clinical evidence of pulmonary edema, pleural effusion, pericardial effusion, or ascites attributed to a cardiac origin by a board-certified cardiologist. Chi-square tests revealed statistically significant differences in presentation between different days of the week, with Thursday being the most common day, and between different hours of the day, with the peak between 10am to 4pm. Evaluation of presentation for CHF by season of the year identified more cats in December, January, and February although this did not achieve statistical significance. No significant difference was identified for presentation based on the day of the month or the month of the year. Conclusions In this population of cats, there was daily, weekly and, possibly, seasonal variation in the frequency of presentation of cats with CHF. Additional studies are warranted to confirm these findings and to determine the cause for these differences. [ABSTRACT FROM AUTHOR]

Objective—To describe the relative importance of pets' quality versus quantity of life among owners of dogs with heart disease. Design—Prospective questionnaire-based clinical study. Sample Population—Owners of 201 dogs with heart disease. Procedures—Owners each completed a questionnaire that was designed to ascertain the relative importance of quality versus quantity of life for their pet and to assess the owners' willingness to trade survival time for quality of life, if that were possible. Analyses were performed to evaluate factors associated with owner willingness to trade time for quality of life. Results—Most owners (170/197 186%]) were willing to trade survival time for quality of life for their heart disease-affected dogs; of those owners, 88 (52%) were willing to trade 6 months. Owners were highly concerned with detection of perceived pet suffering and their pet's ability to interact with them. Owners whose pets had respiratory difficulty or fainting episodes and were treated on an outpatient basis had a greater willingness to trade survival time than owners of dogs that were treated on an emergency basis. Among owners willing to trade time for quality of life, younger owners and those whose pets had fainting episodes were willing to trade the most amount of time. Conclusions and Clinical Relevance—Results indicated that quality of life is highly important to owners of dogs with heart disease. Owners' priorities partly depend on owner age and the pet's clinical circumstances; ongoing client-veterinarian communication is important to optimize treatment success as perceived by owners. [ABSTRACT FROM AUTHOR]

Objective--To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats. Animals--7 healthy neutered male client-owned cats. Procedures--Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and brood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration. Results--2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 ± 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 ± 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 ± 142 ng/mL and 62.4 ± 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration. Conclusions and Clinical Relevance--Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol. [ABSTRACT FROM AUTHOR]

Abstract: The crystalline structure of a 7Li and 11B labeled lithium borohydride has been investigated using neutron powder diffraction at 3.5, 360, and 400K. The B–H bond lengths and H–B–H angles for the [BH4]− tetrahedra indicated that the tetrahedra maintained a nearly ideal configuration throughout the temperature range investigated. The atomic displacement parameters at 360K suggest that the [BH4]− tetrahedra become increasingly disordered as a result of large amplitude librational and reorientational motions as the orthorhombic to hexagonal phase transition (T=384K) is approached. In the high-temperature hexagonal phase, the [BH4]− tetrahedra displayed extreme disorder about the trigonal axis along which they are aligned. Neutron vibrational spectroscopy data were collected at 5K over an energy range of 10–170meV, and were found to be in good agreement with prior Raman and low-resolution neutron spectroscopy studies. [Copyright &y& Elsevier]

Objective-To develop and evaluate a questionnaire (functional evaluation of cardiac health IFETCHI questionnaire) for assessing health-related quality of life in dogs with cardiac disease. Design-Prospective study. Animals-360 dogs with cardiac disease. Procedure-The questionnaire was developed on the basis of widely accepted clinical signs of cardiac disease in dogs. A FETCH score was calculated by summing responses to questionnaire items; possible scores ranged from 0 to 85. For questionnaire validation, owners of 60 dogs were asked to complete the questionnaire and provide an overall assessment of their dogs' quality of life (16 owners completed the questionnaire twice). Disease severity was assessed with the International Small Animal Cardiac Health Council (ISACHC) classification for cardiac disease. Following validation, the final questionnaire was administered to owners of the remaining 300 dogs. Results-Internal consistency of the questionnaire was good, and the FETCH score was significantly correlated with the owner-reported quality-of-life score arid with ISACHC classification. For owners that completed the questionnaire twice, scores were significantly correlated. During the second phase of the study, the FETCH score ranged from 0 to 70 (median, 7) and was significantly correlated with ISACHC classification, but did not vary significantly with underlying disease. For dogs examined twice, the change in FETCH score was significantly greater for dogs in which ISACHC classification improved than for dogs in which ISACHC classification was unchanged. Conclusions and Clinical Relevance-Results suggest that the FETCH questionnaire is a valid and reliable method for assessing health-related quality of life in dogs with cardiac disease. [ABSTRACT FROM AUTHOR]

Tyrosine kinases play a prominent role in human cancer, yet the oncogenic signaling pathways driving cell proliferation and survival have been difficult to identify, in part because of the complexity of the pathways and in part because of low cellular levels of tyrosine phosphorylation. In general, global phosphoproteomic approaches reveal small numbers of peptides containing phosphotyrosine. We have developed a strategy that emphasizes the phosphotyrosine component of the phosphoproteome and identifies large numbers of tyrosine phosphorylation sites. Peptides containing phosphotyrosine are isolated directly from protease-digested cellular protein extracts with a phosphotyrosine-specific antibody and are identified by tandem mass spectrometry. Applying this approach to several cell systems, including cancer cell lines, shows it can be used to identify activated protein kinases and their phosphorylated substrates without prior knowledge of the signaling networks that are activated, a first step in profiling normal and oncogenic signaling networks. [ABSTRACT FROM AUTHOR]

Objective—To determine the dietary patterns and intake of nutrients of concern in dogs with cardiac disease. Design—Prospective study. Animals—82 dogs with dilated cardiomyopathy (DCM) or chronic valvular disease. Procedure—Owners of dogs were contacted and given a standardized telephone questionnaire regarding diet and a 24-hour food recall to determine daily intake of calories, protein, fat, sodium, potassium, and magnesium. Results—Among the 82 dogs, 71% had no congestive heart failure (CHF), and 29% had CHF or a history of CHF. Sixty-one percent of dogs had concurrent diseases. Anorexia was or had been evident in 34% of dogs and was significantly more common in the CHF group and in dogs with DCM. Most dogs (92%) received some treats and table food, with a median percentage of daily calories from treats of 19% (range, 0% to 100%). Most owners (57%) that administered pills used human or pet foods for pill administration. Most dogs ate more than the Association of American Feed Control Officials (AAFCO) minimum values for fat and protein. Daily sodium intake varied from 14 to 384 mg/100 kcal, compared with the AAFCO minimum of 17 mg/100 kcal. A median of 25% of total daily sodium came from treats and table food (range, 0% to 100%). Dogs with CHF ate significantly more sodium, compared with dogs with no CHF. Conclusions and Clinical Relevance—Dietary intake for dogs with cardiac disease is highly variable and often not optimal. [ABSTRACT FROM AUTHOR]

A need exists for technologies that permit the direct quantification of differences in protein and post-translationally modified protein expression levels. Here we present a strategy for the absolute quantification (termed AQUA) of proteins and their modification states. Peptides are synthesized with incorporated stable isotopes as ideal internal standards to mimic native peptides formed by proteolysis. These synthetic peptides can also be prepared with covalent modifications (e.g., phosphorylation, methylation, acetylation, etc.) that are chemically identical to naturally occurring post-translational modifications. Such AQUA internal standard peptides are then used to precisely and quantitatively measure the absolute levels of proteins and post-translationally modified proteins after proteolysis by using a selected reaction monitoring analysis in a tandem mass spectrometer. In the present work, the AQUA strategy was used to (i) quantify low abundance yeast proteins involved in gene silencing, (ii) quantitatively determine the cell cycle-dependent phosphorylation of Ser-1126 of human separase protein, and (iii) identify kinases capable of phosphorylating Ser-1501 of separase in an in vitro kinase assay. The methods described here represent focused, alternative approaches for studying the dynamically changing proteome. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objectives Animals Methods Results Conclusions and Clinical Importance Hypercoagulability has been documented in cats with cardiac disease. However, hemostatic parameters, including viscoelastic coagulation monitoring (VCM) have not been reported in cats with arterial thromboembolism (ATE).Compare VCM parameters in cats with acute cardiogenic ATE and in control cats.Sixteen cats with ATE and 30 control cats.Multicenter university‐based prospective study. Cardiogenic ATE was diagnosed based on physical examination and by ultrasonographically‐diagnosed left atrial enlargement. Viscoelastic coagulation monitor analysis, CBC, serum biochemistry profile and coagulation profile were performed at admission in cats with ATE. Analysis from healthy control cats was performed using blood collected by direct venipuncture. Our objective was comparison of VCM parameters clot time (CT), clot formation time (CFT), alpha angle (Angle), maximum clot formation (MCF), amplitude at 10 and 20 minutes (A10 and A20, respectively) and clot lysis index at 30 and 45 minutes (LI30 and LI45, respectively) between ATE and control cats.Cats with ATE had a decreased angle compared to control cats, with a median (range) of 43° (30‐48°) compared to 47° (14‐59°; P = .01). The parameters A10, A20 and MCF were decreased in ATE cats compared to control cats with a median (range) of 19 units (8–32) compared to 22 units (6–38), 24.5 units (11‐40) compared to 29 units (10‐47) and 29.5 units (13‐44) compared to 33.5 units (14‐53), respectively (P = .01, .01 and .01, respectively). The parameters CT, CFT, LI30 and LI45 were similar between groups (P = .22, .09, .62 and .34, respectively).Cats with cardiogenic ATE cats have VCM parameters consistent with hypocoagulability compared with healthy cats. [ABSTRACT FROM AUTHOR]

Background: Apparently healthy dogs of various breeds eating nontraditional, high‐pulse diets can have larger left ventricular diameter, lower systolic function, and more ventricular premature complexes (VPCs) compared with dogs eating traditional, low‐pulse diets. It is unknown whether Irish Wolfhounds eating high‐pulse diets have similar cardiac abnormalities. Hypothesis/Objectives: To compare electrocardiographic and echocardiographic findings between Irish Wolfhounds eating high‐ or low‐pulse diets. Animals: Ninety‐seven Irish Wolfhounds. Methods: Retrospective study of Irish Wolfhounds that had echocardiography performed at dog shows between October 2018 and May 2021. Demographic information, echocardiographic measurements, cardiac rhythm (1‐minute lead II rhythm strip), and main diet were recorded retrospectively. Diets were classified as high‐pulse or low‐pulse based on the presence and location of pulses (peas, lentils, chickpeas, or dry beans) on the ingredient list. Results: Thirty‐five of 97 Irish Wolfhounds (36%) were eating high‐pulse diets and 62 of 97 (64%) were eating low‐pulse diets. There were no significant differences between diet groups in echocardiographic measurements. A significantly higher percentage of dogs in the high‐pulse diet group (6/35 [17%]) had VPCs compared with those in the low‐pulse diet group (1/62 [2%]; effect size = 0.15 [95% confidence interval: 0.004‐0.31]; P =.005). Conclusions and Clinical Importance: In this retrospective study of apparently healthy Irish Wolfhounds, high‐pulse diets were associated with a higher prevalence of VPCs which could represent early cardiac abnormalities. [ABSTRACT FROM AUTHOR]

Presents information from a study which focused on the source and outcome of adolescents and children hospitalized with major depressive disorder (MMD). Details on how depression and disorders were assessed using the Kiddie-Longitudinal Interval follow-up Evaluation (K-LIFE); Information on recurrence and rate of recovery; Reasons why MMD in children and adolescent often have an episodic disorder.

Reports on the phosphorylation of the glucose in Saccharomyces cerevisiae by yeast hexokinase 2. Single tryptic peptide difference; Sequence and size determination; Consensus and in vitro phosphorylation by protein kinase A.

Objective: To describe the indications and clinical response for dogs and cats treated with esmolol. Design: Retrospective case series from 2003 to 2020. Setting: Single university veterinary teaching hospital. Animals: Twenty‐two dogs and 6 cats. Interventions: Animals received either a bolus or bolus and continuous rate infusion of the ultrashort‐acting beta receptor antagonist, esmolol. Measurements and Main Results: Twenty‐two animals were treated for either a supraventricular or sinus tachycardia, 5 were treated for a ventricular tachycardia, and 1 was treated for atrial fibrillation. Esmolol was most frequently used in dogs (N = 9) who had ingested a toxin such as albuterol, amphetamine, or chocolate. Esmolol was administered at median bolus dose of 330 µg/kg (range 10–1000 µg/kg) and continued as a continuous rate infusion in 15 animals at a median dose of 50 µg/kg/min. Defining success as a reduction in heart rate of 20% or greater, esmolol therapy was considered successful in 13 of 28 animals (46%). Animals treated for a toxicosis were more likely to have a successful rate reduction than those treated for other causes (P = 0.006). Nineteen animals survived to discharge. Both treatment success (P = 0.046) and treatment for a toxicosis (P = 0.003) were associated with survival. Conclusions: Esmolol administration was well tolerated by dogs and cats with tachycardia due to intoxication. Heart rate reduction by at least 20% was achieved in 46% of cases. Animals with toxin ingestion were more likely to be discharged from the hospital. [ABSTRACT FROM AUTHOR]

Presents news briefs in the scientific field as of April 2006. Death of Robert S. Carter, retired Director of the U.S. National Bureau of Standards' Research Reactor Center; Progress of the construction of the Spallation Neutron Source at Oak Ridge National Laboratory in Oak Ridge, Tennessee

Presents a veterinary case report that illustrates the difficulty in differentiating between ventricular tachycardia and wide complex tachycardias of supraventricular origin in dogs. Electrocardiogram (ECG) evaluation; Characterization of the two types of tachycardias in ECG tracings.

Objective: To determine in adult chickens which of 3 CPR techniques, sternal compressions (SC), SC with interposed caudal coelomic compressions (ICCC), or lateral compressions (LC), results in the highest mean systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as measured directly from the carotid artery. Design: Prospective, nonblinded, experimental crossover study. Setting: University teaching hospital laboratory. Animals: Ten retired laying hens. Interventions: Birds were sedated, anesthetized, and placed in dorsal recumbency. A carotid artery catheter was placed to directly measure arterial pressure. Ventricular fibrillation was induced with direct cardiac stimulation using a 9‐Volt battery. Each bird then received 2 minutes of the 3 different cardiac compression techniques in a random order by 3 different compressors, with the compressor order also randomized. Birds were subsequently administered IV epinephrine, and transthoracic defibrillation was attempted. At the end of experimentation, each bird was euthanized, and simple gross necropsies were performed. Linear mixed models followed by pairwise paired t‐tests were performed to evaluate differences in pressures generated by each technique. Measurements and Main Results: The primary study outcomes were SAP, DAP, and MAP over 2 minutes of compressions for each compression technique. Pressures from ICCC (SAP: 27.6 ± 5.3 mm Hg, DAP: 18.7 ± 5.2 mm Hg, MAP: 21.7 ± 5.2 mm Hg) were significantly higher than those from LC (SAP: 18.9 ± 5.4 mm Hg, DAP: 11.6 ± 4.1 mm Hg, MAP: 14.1 ± 4.5 mm Hg). Pressures from SC (SAP: 24.5 ± 6.4 mm Hg, DAP: 15.2 ± 4.3 mm Hg, MAP: 18.3 ± 5.0 mm Hg) were not significantly different from ICCC or LC. Conclusions: External compressions can generate detectable increases in arterial pressure in chickens with ventricular fibrillation. SC with ICCC generated significantly higher arterial pressures than LC. SC alone generated blood pressures that were not significantly different from those generated by SC with ICCC or LC. [ABSTRACT FROM AUTHOR]

Background: The United States Food and Drug Administration is investigating possible diet‐associated dilated cardiomyopathy (DCM) in dogs and cats. Objectives: To retrospectively review DCM cases for signalment, diet information, echocardiographic changes, and survival. Animals Client‐owned dogs (n = 71). Methods: Medical records of dogs diagnosed with DCM between January 1, 2014 and September 30, 2018 were reviewed. Dogs were grouped into "traditional" or "nontraditional" diet categories and whether or not diet was changed after diagnosis. Results: For dogs eating nontraditional diets, those that had their diets changed had a larger percentage decrease in normalized systolic left ventricular internal dimension (P =.03) and left atrial:aorta ratio (P <.001) compared to those that did not have their diets changed. Survival time was significantly longer for dogs with DCM eating nontraditional diets that had their diets changed (median survival, 337 days; range, 9‐1307 days) compared to dogs eating nontraditional diets that did not have their diets changed (median survival, 215 days; range, 1‐852 days; P =.002). Conclusions and Clinical Importance: Dogs with DCM eating nontraditional diets can experience improvement in cardiac function after diet change but additional research is needed to examine possible associations between diet and DCM. [ABSTRACT FROM AUTHOR]

Background: Low vitamin D concentrations have been associated with advanced heart disease and poorer outcomes in people and dogs. Vitamin D status typically is assessed by serum 25(OH)D concentration. However, cats also produce notable amounts of a C‐3 epimer of 25(OH)D (3‐epi). Hypothesis/Objectives: Determine if vitamin D status, estimated by 25(OH)D3 alone or combined with 3‐epi (summation vitD), is lower in cats with cardiomyopathy (CM) compared to clinically normal (N) cats and if indicators of disease severity are associated with vitamin D status. Animals Privately owned cats, 44 with CM and 56 N. Methods: Cross‐sectional observational study using clinical and echocardiographic findings, diet history, and serum 25(OH)D3 and 3‐epi measurements. Results: Cat age was negatively related to vitamin D status. Summation vitD was lower in CM cats (median = 47.1 ng/mL) compared to N cats (median = 58.65 ng/mL) both before (P =.03) and after (P =.04) accounting for age. However, 25(OH)D3 became nonsignificant between CM and N cats after age was included. Summation vitD was related positively to survival time and fractional shortening (FS), but negatively to left atrial enlargement (LAE) severity, both before and after accounting for age. For 25(OH)D3 alone, only survival time and FS remained significant after including age. Conclusions and Clinical Importance: We report 25(OH)D3 and 3‐epi concentrations in CM and N cats. Age had an important (negative) relationship to vitamin D status. After accounting for age, summation vitD was lower in CM cats. Vitamin D status was related positively to survival time and FS, but negatively to LAE severity. [ABSTRACT FROM AUTHOR]

Background: Cardiac cachexia is common in people and dogs with congestive heart failure (CHF). However, the prevalence and effects of cardiac cachexia in cats are unknown. Objectives: To determine the prevalence of cachexia and its associations with clinical laboratory and survival data in cats with CHF. Animals: One hundred twenty‐five cats with CHF. Methods: Medical records of cats evaluated during a 40‐month period were retrospectively reviewed to identify cats with cardiac cachexia using 7 different definitions. Clinical, laboratory, and survival data were compared between cats with and without cachexia. Results: Prevalence of cachexia ranged from 0 to 66.7% for the 7 definitions, with a prevalence of 41.6% using muscle condition score (MCS). Cats with cachexia (determined by MCS) were older (P <.001), more likely to have pleural effusion (P =.003), had significantly higher blood urea nitrogen (P <.001) and neutrophil concentrations (P =.01), and significantly lower body condition score (P <.001), body weights (P <.001), hematocrit (P =.007), and hemoglobin concentrations (P =.009). Survival time for cats with cachexia (determined by MCS) was significantly shorter than for cats without cachexia (P =.03). Cats that were underweight (P =.002) and cats with dilated cardiomyopathy (DCM) also had shorter survival times (P =.04). Conclusions and Clinical Importance: The association between cachexia and reduced survival time emphasizes the importance of identifying and addressing this common problem in cats with CHF. [ABSTRACT FROM AUTHOR]

Background: Cardiac cachexia, loss of muscle mass associated with congestive heart failure (CHF), is associated with increased morbidity and shorter survival times in people, but an association between cardiac cachexia and survival has not been reported in dogs. Objectives: To determine the prevalence of cachexia and its associations with clinical, laboratory, and survival data in dogs with CHF. Animals: Two hundred sixty‐nine dogs with CHF. Methods: Retrospective cohort study. Cachexia was defined by 1 of 2 definitions: (1) mild, moderate, or severe muscle loss or (2) weight loss of ≥5% in 12 months or less. Variables were compared between dogs with and without cachexia. Results: One hundred thirty of 269 dogs (48.3%) had cardiac cachexia based on muscle loss, whereas 67 of 159 dogs (42.1%) with pre‐evaluation body weights had cachexia based on weight loss. Dogs with cachexia (based on muscle loss) were significantly older (P =.05), more likely to have a cardiac arrhythmia (P =.02), had higher chloride concentrations (P =.04), and had a lower body condition score (P < .001), hematocrit (P =.006), hemoglobin (P =.006), and albumin (P =.004) concentrations. On multivariable analysis, cachexia (P =.05), clinically important tachyarrhythmias (P < .001), azotemia (P < .001), and being under‐ or overweight (both P =.003) were associated with shorter survival times. Conclusions and Clinical Importance: Cardiac cachexia in common in dogs with CHF and is associated with significantly shorter survival. This emphasizes the importance of preventing, diagnosing, and treating muscle loss in dogs with CHF. [ABSTRACT FROM AUTHOR]

Low-temperature neutron scattering spectra of diammonium dodecahydro-closo-dodecaborate [(NH4)2B12H12] reveal two NH4+ rotational tunneling peaks (e.g., 18.5 μeV and 37 μeV at 4 K), consistent with the tetrahedral symmetry and environment of the cations. The tunneling peaks persist between 4 K and 40 K. An estimate was made for the tunnel splitting of the first NH4+ librational state from a fit of the observed ground-state tunnel splitting as a function of temperature. At temperatures of 50 K-70 K, classical neutron quasi-elastic scattering appears to dominate the spectra and is attributed to NH4+ cation jump reorientation about the four C3 axes defined by the N-H bonds. A reorientational activation energy of 8.1 ± 0.6 meV (0.79 ± 0.06 kJ/mol) is determined from the behavior of the quasi-elastic linewidths in this temperature regime. This activation energy is in accord with a change in NH4+ dynamical behavior above 70 K. A low-temperature inelastic neutron scattering feature at 7.8 meV is assigned to a NH4+ librational mode. At increased temperatures, this feature drops in intensity, having shifted entirely to higher energies by 200 K, suggesting the onset of quasi-free NH4+ rotation. This is consistent with neutron-diffraction-based model refinements, which derive very large thermal ellipsoids for the ammonium-ion hydrogen atoms at room temperature in the direction of reorientation. [ABSTRACT FROM AUTHOR]

To ensure survival in the face of genomic insult, cells have evolved complex mechanisms to respond to DNA damage, termed the DNA damage checkpoint. The serine/threonine kinases ataxia telangi- ectasia-mutated (ATM) and ATM and Rad3-related (ATR) activate checkpoint signaling by phosphorylating substrate proteins at SQ/TQ motifs. Although some ATM/ATR substrates (Chk1, p53) have been identified, the lack of a more complete list of substrates limits current understanding of checkpoint pathways. Here, we use immunoaffinity phosphopeptide isolation coupled with mass spectrometry to identify 570 sites phosphorylated in UV-damaged cells, 498 of which are previously undescribed. Semiquantitative analysis yielded 24 known and 192 previously uncharacterized sites differentially phosphorylated upon UV damage, some of which were confirmed by SILAC, Western blotting, and immunoprecipitation/ Western blotting. ATR-specific phosphorylation was investigated by using a Seckel syndrome (ATR mutant) cell line. Together, these results provide a rich resource for further deciphering ATM/ATR signaling and the pathways mediating the DNA damage response. [ABSTRACT FROM AUTHOR]

A response by Madhukar H. Trivedi, A. John Rush and Stephen R. Wisniewski to a letter to the editor about his article the remission rates of Sequenced Treatment Alternatives to Relieve Depression in the 2006 issue is presented.

Presents information on a study that determined the prevalence of anorexia and the dietary patterns of dogs with cardiac disease. Role of nutrition in the management of patients with cardiac disease; Nutritional alterations of dogs with cardiac disease; Variety of nutritional modifications that have been proposed to slow progression of the disease.

Objective: To determine if human automated external defibrillators (AEDs) could successfully record cardiac electrical activity in dogs, make appropriate recommendations regarding shock delivery, and characterize skin preparation required for a readable ECG based on dog haircoat characteristics. Design: Prospective study of AED use in dogs conducted between January and March 2021. Setting: University teaching hospital. Animals: Three groups of client‐owned dogs were evaluated. Group 1 consisted of 23 healthy dogs with sinus rhythms, group 2 consisted of 9 dogs with documented cardiac arrhythmias, and group 3 consisted of 9 dogs receiving CPR following naturally occurring cardiopulmonary arrest. Materials and Methods: Haircoat characteristics and clipping or ECG paste required to obtain a readable ECG were recorded. The time interval from a readable ECG by the investigator until AED shock advisement was measured. Correctness of shock advice was recorded. Analyses were performed using commercial statistical software. P‐values <0.05 were considered significant. Results: The attending veterinarian judged the ECG on the AED to be readable in all dogs. Time to shock advisement in all dogs was median 18 (range: 7–180) seconds. Dogs with heavy, long, or double haircoats required clipping in 24 of 27 (89%) cases to obtain a readable ECG. ECG paste on the AED pad was required in 36 of 40 dogs (90%) in order to obtain a readable ECG. The AED advice for delivery of shock was appropriate in 51 of 52 (98%) queries of the machine across all groups. Conclusions: Human AEDs can successfully record cardiac electrical activity in dogs. AEDs appropriately recommend delivery of a shock most times, contingent on skin preparation. Dogs with double, long, or heavy haircoats should be clipped prior to pad application. ECG paste will aid AED reading in all haircoat types. Further investigation is warranted into AED use in dogs, particularly in general practices. [ABSTRACT FROM AUTHOR]

Objective To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis. Case Series Summary This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing. New or Unique Information Provided This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol. [ABSTRACT FROM AUTHOR]

Presents a response by Lisa M. Freeman and colleagues to a letter to the editor about their article on the quality of life of dogs with heart disease.

OBJECTIVE To compare metabolomic profiles of dogs eating grain-free (GF) versus grain-inclusive (GI) diets (1) for healthy dogs at baseline and (2) for dogs with subclinical cardiac abnormalities at 12 months after a diet change. SAMPLE Serum samples from 23 dogs eating GF diets and 79 dogs eating GI diets, of which 17 (8 eating a GF diet and 9 eating a GI diet) were reevaluated 12 months after a diet change. PROCEDURES Metabolomic profiles were developed by means of ultrahigh-performance liquid chromatography–tandem mass spectroscopy of serum samples. Baseline results for the GF group were compared with those for the GI group. Dogs from both groups with subclinical cardiac abnormalities were transitioned to a GI, pulse-free, intervention diet, and samples collected 12 months later were compared between diet groups. Statistical significance for biochemical group differences was defined as P < .05 with a false discovery rate (q) < .10. RESULTS Baseline differences in lipid metabolism and amino acid metabolism were found between the GF and GI diet groups. There were 46 metabolites that were higher and 82 metabolites that were lower in the GF group (n = 23), compared with the GI group (79). Comparison of the GF (n = 8) and GI (9) groups 12 months after the diet change showed only 6 metabolites that were higher and 11 metabolites that were lower in the GF group, compared with the GI group. CLINICAL RELEVANCE Metabolomic pathway differences between dogs eating GF versus GI diets highlight the important effect of diet in metabolomics analyses. The clinical importance of these differences and how they might relate to cardiac disease in dogs remains undetermined. [ABSTRACT FROM AUTHOR]

Objective - To describe a case of acute tracheal compression due to a dorsal tracheal membrane abscess in a dog. Case Summary - A 3-year-old intact male Bluetick Coonhound presented for evaluation of 36 hours of marked inspiratory dyspnea and stridor. A radiographic diagnosis of tracheal collapse was made on thoracic radiographs, which was confirmed to be static compression by tracheoscopy. Dorsal extraluminal tracheal compression from a fluid filled structure adjacent to the trachea was suspected based on ultrasonography. Endoscopic-guided transtracheal fine needle aspiration yielded septic suppurative inflammation. At surgery an abscess in the dorsal tracheal membrane was identified, lanced, and lavaged, which resulted in restoration of normal tracheal diameter. The dog developed bilateral pneumothorax, which was treated medically by thoracostomy tube placement and manual evacuation of the accumulated air. Postoperative radiographs also revealed evidence of pneumomediastinum. Pneumothorax and pneumomediastinum likely occurred secondary to the surgical approach, worsened by positive pressure ventilation. Cultures of the abscess isolated a nonhemolytic Streptococcus species but with no evidence of anaerobic bacteria. The dog made a full functional recovery. New or Unique Information Provided - Tracheal compression is a rare diagnosis in dogs. To the authors' knowledge, this represents the first report of an abscess in the dorsal tracheal membrane, diagnosed by endoscopic-guided transtracheal fine needle aspiration, causing clinically relevant acute tracheal obstruction. [ABSTRACT FROM AUTHOR]

Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences. [ABSTRACT FROM AUTHOR]

Background: A recent study showed higher high‐sensitivity cardiac troponin I (hs‐cTnI) concentrations in healthy dogs eating grain‐free (GF) compared to those eating grain‐inclusive (GI) diets. Hypothesis/Objectives: Healthy dogs with subclinical cardiac abnormalities eating GF diets at baseline will show improvements in cardiac biomarkers and echocardiographic variables after diet change, whereas healthy dogs eating GI diets at baseline will not improve. Animals: Twenty healthy dogs with subclinical cardiac abnormalities (12 Golden Retrievers, 5 Doberman Pinschers, 3 Miniature Schnauzers). Methods: This prospective study included dogs with increased hs‐cTnI or N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) concentrations, or echocardiographic abnormalities. Mixed modeling was used to evaluate echocardiographic, hs‐cTnI, and NT‐proBNP differences between groups (GF or GI diet at baseline) over time (1 y after diet change). Results: Ten GF and 10 GI dogs were evaluated. There were statistically significant time: group interactions for hs‐cTnI (P =.02) and normalized left ventricular internal systolic diameter (LVIDsN; P =.02), with GF dogs showing larger decreases in these variables than GI dogs. Median (range) hs‐cTnI (ng/mL) for GF dogs was 0.141 (0.012‐0.224) at baseline and 0.092 (0.044‐0.137) at 1 y, and for GI dogs was 0.051 (0.016‐0.195) at baseline and 0.060 (0.022‐0.280) at 1 y. Median LVIDsN for GF dogs was 1.01 (0.70‐1.30) at baseline and 0.87 (0.79‐1.24) at 1 y, and for GI dogs was 1.05 (0.84‐1.21) at baseline and 1.10 (0.85‐1.28) at 1 y. Conclusions and Clinical Importance: Decreased hs‐cTnI and LVIDsN in GF dogs after diet change supports reversibility of these subclinical myocardial abnormalities. [ABSTRACT FROM AUTHOR]