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Hair cortisol concentration (HCC) is being used increasingly to evaluate long‐term stress in many mammalian species. Most of the cortisol is assumed to passively diffuse from circulating blood into hair follicles and gradually accumulate in growing hair. However, our research with free‐ranging grizzly bears (Ursus arctos) suggests HCC increases significantly within several hours following capture, a time too brief to be explained by this mechanism alone. In this study with captive grizzly bears, we sought to determine if a brief spike in blood cortisol concentration, thus mimicking a single stressful event, would cause an increase in HCC over a 7‐day period. To do this, we administered a single intravenous dose (5 μg/kg) of cosyntropin to three captive unanaesthetised adult female grizzly bears on two occasions, during April when hair growth was arrested and during August when hair was growing. In both trials, the cosyntropin caused a two‐fold or greater increase in serum cortisol levels within 1 hr but did not appear to influence HCC at 1, 48, and 168 hr following cosyntropin administration. We conclude the cosyntropin‐induced cortisol spike was likely insignificant when compared to the adrenocortical response that occurs in free‐ranging bears when captured. We suggest further study with a larger sample of captive bears to evaluate the combined effects of anaesthesia and multiple doses of cosyntropin administered over several hours would better simulate the adrenocortical response of free‐ranging grizzly bears during capture., Administration of cosyntropin to captive grizzly bears caused increased serum cortisol levels within 1 hr. However, cosyntropin did not influence hair cortisol concentration at 1, 48, and 168 hr following administration. Cosyntropin‐induced hair cortisol levels were insignificant compared to free‐ranging bears during capture.

Across China and Southeast Asia, over 17,000 bears are currently farmed for bile, predominantly for traditional Chinese medicines. Bears on farms in China are cage confined and undergo repeated daily bile extraction facilitated by surgically implanted catheters or gallbladder fistulas. Numerous health problems have been reported in bile-farmed bears including peritonitis, abdominal hernias, and extraction site abscessation. Between 2009 and 2014, five Asiatic black bears ( Ursus thibetanus) and one Asiatic black/Eurasian brown bear ( Ursus arctos arctos) hybrid, rescued from the bear bile industry in China, died from ruptured and/or dissecting aortic aneurysm. Medical records were reviewed and two bears exhibited no clinical signs prior to death. In four bears, clinical findings varied and included increased stereotypic behavior prior to death, epistaxis, retinal lesions, dysphagia, weight loss, and acute onset of hyporexia. On postmortem examination, hemopericardium with dissection and/or rupture of the ascending aorta and left ventricular wall hypertrophy were present in all cases. No evidence of infectious disease, connective tissue disorders, or congenital cardiac disease was identified. Based on these observations screening thoracic radiography was performed on all bears at the rescue center and aortic dilation was identified in 73 of 134 (54.5%) bile-extracted bears. To the authors' knowledge, aortic aneurysm, rupture, and/or dissection have not been previously reported in any bear species and the high prevalence in this population of bears suggests an association with bile-farming practices. Future studies are needed to investigate the etiopathogenesis of this condition to aid in early diagnosis and improved management of bears being rescued from bile farms across Asia.

The fukutin-related protein P448L mutant mouse replicates many pathologies common to limb girdle muscular dystrophy 2i (LGMD2i) and is a potentially strong candidate for relevant drug screening studies. Because striated muscle function remains relatively uncharacterized in this mouse, we sought to identify metabolic, functional and histological metrics of exercise and cardiac performance. This was accomplished by quantifying voluntary exercise on running wheels, forced exercise on respiratory treadmills and cardiac output with echocardiography and isoproterenol stress tests. Voluntary exercise revealed few differences between wild-type and P448L mice. By contrast, peak oxygen consumption (VO2peak) was either lower in P448L mice or reduced with repeated low intensity treadmill exercise while it increased in wild-type mice. P448L mice fatigued quicker and ran shorter distances while expending 2-fold more calories/meter. They also received over 6-fold more motivational shocks with repeated exercise. Differences in VO2peak and resting metabolic rate were consistent with left ventricle dysfunction, which often develops in human LGMD2i patients and was more evident in female P448L mice, as indicated by lower fractional shortening and ejection fraction values and higher left ventricle systolic volumes. Several traditional markers of dystrophinopathies were expressed in P448L mice and were exacerbated by exercise, some in a muscle-dependent manner. These include elevated serum creatine kinase and muscle central nucleation, smaller muscle fiber cross-sectional area and more striated muscle fibrosis. These studies together identified several markers of disease pathology that are shared between P448L mice and human subjects with LGMD2i. They also identified novel metrics of exercise and cardiac performance that could prove invaluable in preclinical drug trials.NEW & NOTEWORTHY Limb-girdle muscular dystrophy 2i is a rare dystroglycanopathy that until recently lacked an appropriate animal model. Studies with the FKRP P448L mutant mouse began assessing muscle structure and function as well as running gait. Our studies further characterize systemic muscle function using exercise and cardiac performance. They identified many markers of respiratory, cardiac and skeletal muscle function that could prove invaluable to better understanding the disease and more importantly, to preclinical drug trials.

Recent studies suggest that bears have relatively high cognitive capabilities. However, cognitive processes and problem-solving abilities remain relatively unexplored in bear species. We studied the capacity for 8 captive brown bears ( Ursus arctos ) to move and use inanimate objects to obtain a food reward. We recorded their behaviors during the problem-solving process using a behavioral ethogram. Three items, a large log, a small log, and a box, were placed in an outdoor enclosure. As the bears progressed through 3 stages of trials, they would need to manipulate the objects and displace them into the proper location and orientation to climb atop to reach a suspended food reward. Completion of the third and final stage was deemed to be evidence of tool use. Six of the 8 bears were capable of tool use. Most bears (>90% of trials) were successful in completing the final stage in

Training nonhuman animals in captivity for participation in routine husbandry procedures is believed to produce a lower stress environment compared with undergoing a general anesthetic event for the same procedure. This hypothesis rests largely on anecdotal evidence that the captive subjects appear more relaxed with the trained event. Blood markers of physiological stress responses were evaluated in 4 captive grizzly bears (Ursus arctos horribilis) who were clicker-trained for blood collection versus 4 bears who were chemically immobilized for blood collection. Serum cortisol and immunoglobulin A (IgA) and plasma β-endorphin were measured as indicators of responses to stress. Plasma β-endorphin was not different between the groups. Serum IgA was undetectable in all bears. Serum cortisol was undetectable in all trained bears, whereas chemically immobilized bears had marked cortisol elevations (p .05). The highest cortisol elevations were found in 2 bears with extensive recent immobilization experience. These findings support the use of positive reinforcement training for routine health procedures to minimize anxiety.

Increased land use by polar bears (Ursus maritimus) due to climate‐change‐induced reduction of their sea‐ice habitat illustrates the impact of climate change on species distributions and the difficulty of conserving a large, highly specialized carnivore in the face of this global threat. Some authors have suggested that terrestrial food consumption by polar bears will help them withstand sea‐ice loss as they are forced to spend increasing amounts of time on land. Here, we evaluate the nutritional needs of polar bears as well as the physiological and environmental constraints that shape their use of terrestrial ecosystems. Only small numbers of polar bears have been documented consuming terrestrial foods even in modest quantities. Over much of the polar bear's range, limited terrestrial food availability supports only low densities of much smaller, resident brown bears (Ursus arctos), which use low‐quality resources more efficiently and may compete with polar bears in these areas. Where consumption of terrestrial foods has been documented, polar bear body condition and survival rates have declined even as land use has increased. Thus far, observed consumption of terrestrial food by polar bears has been insufficient to offset lost ice‐based hunting opportunities but can have ecological consequences for other species. Warming‐induced loss of sea ice remains the primary threat faced by polar bears.

The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition.

Global warming has the potential to reduce arctic sea ice and thereby increase the length of summer–fall fasting when polar bears (Ursus maritimus) lose access to most marine mammals. To evaluate the consequences of such changes, we compared the cost of fasting by polar bears with hibernation by brown bears (U. arctos), American black bears (U. americanus), and polar bears and made projections about tissue reserves polar bears will need to survive and reproduce as fasts become longer. Hibernating polar bears expend energy at the same rate per unit mass as do brown bears and black bears. However, daily mass losses, energy expenditures, and the losses of lean mass are much higher in fasting, active polar bears than in hibernating bears. The average pregnant polar bear living around Hudson Bay during the 1980s and 1990s could fast for 10.0 6 2.3 months (¯ X 6 SD), and the average lactating female with cubs born during the preceding winter could fast for 4.2 6 1.9 months. Thus, some pregnant or lactating females with lower levels of body fat content were already approaching or beyond the constraint of being able to produce cubs and survive the required 8 months of fasting if producing new offspring or 4 months if accompanied by older offspring. Pregnant or lactating females and their dependent offspring have the most tenuous future as global warming occurs. Thus, we predict a significant reduction in productivity with even modest increases in global warming for polar bears living in the very southern part of their range and are concerned about more northern populations depending on their ability to accumulate increasing amounts of fat.

The number, size, and survival of bear cubs emerging from winter dens depend on maternal condition prior to entering the den. We hypothesized that delayed implantation provides flexibility in timing of birth such that pregnant females are able to track environmental or body conditions long after conception to optimize reproductive output in a changing environment. We tested the hypotheses that causative links between maternal condition and size of newly emerging brown bear (Ursus arctos) cubs were females in superior condition give birth earlier and, thereby, lactate longer in the den than females in poorer condition; and females in superior condition produce more milk or higher quality milk, which accelerates cub growth relative to females in poorer condition. No brown bear with a body fat content 20% produced cubs even though breeding occurred. Brown bears that were fat gave birth earlier than those that were lean. Cubs nursing from fat mothers grew faster than those nursing from lean mothers. The combination of an earlier birth date and faster growth by cubs produced from fat mothers increased mass of brown bear and polar bear (U. maritimus) twins at den emergence by 330– 360 g for each unit increase in percent maternal body fat content when entering hibernation.

The natural aging process results in the physiological decline of multiple tissues and organ systems. Changes commonly occur with middle age and include decreased skeletal muscle mass, bone mineral density, cardiac output, and insulin sensitivity, and increased adiposity, all of which can contribute to the onset of sarcopenia, osteoporosis, heart failure, or type 2 diabetes. Recent studies suggest that myostatin may influence many of these systems. We therefore sought to determine whether they are affected by aging, especially in ‘middle-aged’Mstn−/−mice (12–20 months old (m.o.)). Although body weights were similar in wild-type (WT) andMstn−/−mice, lean fat-free mass and skeletal muscles composed of predominantly type I, II, and mixed fibers were significantly heavier inMstn−/−mice. These differences were accompanied by lower total adiposity, especially in female mice, white and brown fat pad weights, and adipocyte size. Hearts were heavier inMstn−/−mice across a large age range (3–24 m.o.) and exhibited signs of dilated cardiomyopathy at rest, which include lower strain measurements compared with WT myocardium. However,Mstn−/−mice responded better to isoproterenol stress tests with greater increases in fractional shortening and ejection fraction—differences that were again more apparent in females and which are consistent with physiological cardiac hypertrophy. Spleens and kidneys were also smaller, although histologically normal, inMstn−/−mice. These data together suggest that attenuating myostatin could potentially prevent or possibly treat pathological conditions that develop with age. Additional studies are nevertheless needed to definitively assess potential risks to cardiac function.

Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse induced bone loss in bears into novel treatments for osteoporosis.

Although myostatin negatively regulates skeletal muscle growth, its function in heart is virtually unknown. Herein we demonstrate that it inhibits basal and IGF-stimulated proliferation and differentiation and also modulates cardiac excitation–contraction (EC) coupling. Loss of myostatin induced eccentric hypertrophy and enhanced cardiac responsiveness to β-adrenergic stimulation in vivo. This was due to myostatin null ventricular myocytes having larger [Ca2+]i transients and contractions and responding more strongly to β-adrenergic stimulation than wild-type cells. Enhanced cardiac output and β-adrenergic responsiveness of myostatin null mice was therefore due to increased SR Ca2+ release during EC coupling and to physiological hypertrophy, but not to enhanced myofilament function as determined by simultaneous measurement of force and ATPase activity. Our studies support the novel concept that myostatin is a repressor of physiological cardiac muscle growth and function. Thus, the controlled inhibition of myostatin action could potentially help repair damaged cardiac muscle by inducing physiological hypertrophy.

Rationale: The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region. Objective: The purpose of this study was to investigate the contribution of titin’s proline–glutamate–valine–lysine (PEVK) region to biomechanics and growth of the heart. Methods and Results: We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element. Conclusions: Titin’s PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies.

Records were reviewed from 83 cases to determine the main causes and clinical significance of feline pericardial effusion. The most common causes included hypertrophic cardiomyopathy with congestive heart failure, neoplasia, and systemic infection. Most cases had concurrent or secondary pleural effusion or pulmonary edema, with clinical signs of respiratory disease. However, several cases appeared to be affected solely by pericardial effusion rather than pulmonary pathology. Feline pericardial effusion remains an infrequent diagnosis, but its clinical relevance and association with severe cardiac and extracardiac disease warrant diagnostic evaluation.

The accuracy of bioptome placement for endomyocardial biopsy was evaluated using standard fluoroscopic guidance and compared simultaneously with two-dimensional echocardiography in six healthy subadult grizzly bears (Ursus arctos horribilis). Despite perceived adequate positioning of the bioptome toward the septum when judged using fluoroscopy, only one out of the six placements were actually positioned in the right ventricular apex toward the septum when evaluated using two-dimensional echocardiography. The bioptome was readily relocated to the right ventricular apex/septal location by echocardiography. The forceps were easily visualized at all times and the open cups were readily directed into the desired location for biopsy. Based on a subjective score for tissue quantity from 1 to 4 (poor to excellent), biopsies collected by echocardiographic-guided technique had a mean score of 3.4, while biopsies collected by fluoroscopic-guided technique had a mean score of 1.8. In summary, this study suggests that endomyocardial biopsy locations can be accurately positioned using two-dimensional echocardiography with the advantages of less radiation, lower procedural costs, and direct visualization of the sampling site. Clear definition of endocardial surface as afforded by echocardiography may enhance tissue sample quality and lower potential complications from this procedure.

This prospective study was designed to investigate D-dimer concentrations in clinically healthy dogs, clinically ill dogs without thromboembolic disease (TE), and dogs with TE. The goals of this study were to determine whether the coagulation cascade is activated in nonembolic metabolic and inflammatory conditions and whether differentiation from TE is possible. Group 1 consisted of 30 clinically healthy dogs presented for routine care. Group 2 consisted of 67 clinically ill dogs without TE. This group was subdivided into the following categories: postoperative surgical procedures, congestive heart failure, renal failure, hepatic disease, and neoplastic disease. Group 3 consisted of 20 dogs diagnosed with TE. A CBC and a measurement of prothrombin time (PT), activated partial thromboplastin time (PTT), fibrinogen degradation product (FDP) concentration, and plasma D-dimer concentration was performed on dogs in all groups. D-dimer concentrations were highest in dogs with TE; next highest was the hepatic disease group. Only these 2 groups had median D-dimer concentrations markedly different from clinically healthy dogs. The frequency of platelet abnormalities was markedly greater for the TE and neoplastic disease groups. The sensitivity of D-dimer concentrations >500 ng/mL for predicting TE was 100%; however, the specificity of D-dimer for TE at that concentration was 70%. The specificity of D-dimer concentrations >1,000 ng/mL to predict TE was 94% (sensitivity, 80%), and the specificity of D-dimer concentrations >2,000 ng/mL was 98.5% (sensitivity, 36%). FDPs were not high in any TE patient; thus, they may be an insensitive indicator of thromboembolism, with or without overt disseminated intravascular coagulation (DIC).

Grizzly bears (Ursus arctos horribilis) are inactive for up to 6 months during hibernation. They undergo profound seasonal changes in food intake, body mass, and energy expenditure. The circa-annual regulation of metabolism is poorly understood. In the present study, we measured plasma ghrelin, leptin, obestatin, and neuropeptide-Y (NPY) levels, hormones known to be involved in the regulation of energy homeostasis, in ten grizzly bears. Blood samples were collected during the active summer period, early hibernation and late hibernation. Plasma levels of leptin, obestatin, and NPY did not change between the active and the hibernation periods. Plasma total ghrelin and desacyl-ghrelin concentrations significantly decreased during the inactive winter period compared to summer levels. The elevated ghrelin levels may help enhance body mass during pre-hibernation, while the low plasma ghrelin concentrations during hibernation season may contribute to the maintenance of hypophagia, low energy utilization and behavioral inactivity. Our results suggest that ghrelin plays a potential role in the regulation of metabolic changes and energy homeostasis during hibernation in grizzly bears.

The purpose of this study was to explore expectations of athletes and nonathletes about sport psychology consulting. Tinsley's (1982) Expectations About Coun-seling-Brief form was revised using sport psychology terms. The revised instrument, Expectations About Sport Psychology Consulting (EASPC) questionnaire, was administered to 111 athletes (64 male and 47 female) and 166 nonathletes (72 male and 94 female) attending an NCAA Division I university. Confirmatory factor analysis showed that the data fit the hypothesized 3-factor model (i.e., personal commitment, facilitative conditions, and consultant expertise). A 2 (College Sport Participation) 2 (Gender) MANOVA and follow-up discriminant function analyses revealed that females had higher expectancies of personal commitment than did males whereas males believed that consultants were more directive and more capable of solving problems quickly than did females. No significant differences were obtained between athletes and their peers. The results ...

The records of 16 dogs with left ventricular dysfunction associated with severe systemic illness were reviewed. The most common diagnoses in affected dogs were sepsis and cancer. Despite left ventricular dysfunction, no dog presented with signs of congestive heart failure. Fifteen dogs were presented with generalized weakness as a part of their clinical complaint. Twelve (75%) of 16 dogs died or were euthanized within 15 days of admission to the hospital. The average time until death was 3.6 days.

Although the exact incidence of pulmonary thromboembolism (PTE) in small animals is unknown, it is thought that PTE is a substantial, under-diagnosed complication. The difficulty in diagnosing PTE in small animals is confounded by its subtle symptomatic presentation and a lack of clinical suspicion, coexisting disease states, and lack of noninvasive tests that are sensitive and specific for the diagnosis of PTE. Although numerous laboratory markers of coagulation have been studied, only the D-dimer assay has shown clinical utility in detecting early embolism in humans. This paper examines the use of D-dimer assays and other clinical modalities in the diagnostic approach to thromboembolic disease in small animals.

The purpose of this study was to assess the effects of systemic hypertension (SHT) on echocardiographic and radiographic cardiovascular variables in affected cats compared with healthy geriatric cats. Secondary objectives were to determine whether there were any relationships between these findings and age or systolic blood pressure (SBP). Fifteen healthy cats (8 years of age with normal SBP) and 15 hypertensive cats (SBP180 mm Hg) were studied. Each cat was evaluated for standard echocardiographic parameters and 4 different aortic root dimensions. Seventeen variables were measured from right lateral and dorsoventral radiographic views. Left ventricle wall thickness was greater in the SHT group (5.1 +/- 0.9 mm) than in the healthy cats (4.2 +/- 0.5 mm). Left ventricular hypertrophy in the SHT cats often was not severe, and mean measures were considered normal. Some cats had asymmetrical septal hypertrophy (ASH) in the basilar portion of the septum as determined from the 2-dimensional view of the left ventricular outflow tract. ASH was greater in cats with SHT. Comparisons of the proximal ascending aorta indicated the presence of dilatation in the SHT cats, and comparison of the ascending aorta to the aortic annulus was helpful in differentiating between the 2 groups. The distal aortic root measurements and ratios evaluated by echocardiography were significantly different between the 2 groups of cats (P = .0001) and were significantly correlated with SBP (P = .0001) but not age (P.3).