Testing spatial working memory in pigs using an automated T-maze.

Pigs are an important large animal model for translational clinical research but underutilized in behavioral neuroscience. This is due, in part, to a lack of rigorous neurocognitive assessments for pigs. Here, we developed a new automated T-maze for pigs that takes advantage of their natural tendency to alternate. The T-maze has obvious cross-species value having served as a foundation for cognitive theories across species. The maze (17' × 13') was constructed typically and automated with flanking corridors, guillotine doors, cameras, and reward dispensers. We ran nine pigs in (1) a simple alternation task and (2) a delayed spatial alternation task. Our assessment focused on the delayed spatial alternation task which forced pigs to wait for random delays (5, 60, 120, and 240 s) and burdened spatial working memory. We also looked at self-paced trial latencies, error types, and coordinate-based video tracking. We found pigs naturally alternated but performance declined steeply across delays (R2 = 0.84). Self-paced delays had no effect on performance suggestive of an active interference model of working memory. Positional and head direction data could differentiate subsequent turns on short but not long delays. Performance levels were stable over weeks in diverse strains and sexes, and thus provide a benchmark for future neurocognitive assessments in pigs.

Sex and estrous cycle in memory for sequences of events in rats.

The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a two four-odor sequence memory task delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose-port for ≥ 1.2 s; eventually demonstrating sequence memory by holding their nose in the port ≥ 1 s for in-sequence odors and < 1 s for out-of-sequence odors. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to humans performing an analogous task (Reeders et al., 2021). Likewise, no differences in sequence memory performance were found across the estrous cycle. Some caveats are that males acquired out-of-sequence trials faster during training with a 3-odor sequence, but this apparent advantage did not carry over to the 4-odor sequence. Additionally, males had shorter poke times overall which seem consistent with a decreased overall response inhibition because they occurred regardless of sequence demands. Together, these results suggest sex and estrous cycle are not major factors in sequence memory capacities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A lifetime of challenges: real-life decision outcomes in early- and late-onset suicide attempters.

BACKGROUND: People who have attempted suicide display suboptimal decision-making in the lab. Yet, it remains unclear whether these difficulties tie in with other detrimental outcomes in their lives besides suicidal behavior. We hypothesize that this is more likely the case for individuals who first attempted suicide earlier than later in life. METHODS: A cross-sectional case-control study of 310 adults aged ≥ 50 years (mean: 63.9), compared early- and late-onset attempters (first attempt < 55 vs. ≥ 55 years of age) to suicide ideators, non-suicidal depressed controls and non-psychiatric healthy controls. Participants reported potentially avoidable negative decision outcomes across their lifetime, using the Decision Outcome Inventory (DOI). We employed multi-level modeling to examine group differences overall, and in three factor-analytically derived domains labeled Acting Out, Lack of Future Planning, and Hassles. RESULTS: Psychopathology predicted worse decision outcomes overall, and in the more serious Acting Out and Lack of Future Planning domains, but not in Hassles. Early-onset attempters experienced more negative outcomes than other groups overall, in Lack of Future Planning, and particularly in Acting Out. Late-onset attempters were similar to depressed controls and experienced fewer Acting out outcomes than ideators. LIMITATIONS: The cross-sectional design precluded prospective prediction of attempts. The assessment of negative outcomes may have lacked precision due to recall bias. CONCLUSIONS: Whereas early-onset suicidal behavior is likely the manifestation of long-lasting decision-making deficits in several serious aspects of life, late-onset cases appear to function similarly to non-suicidal depressed adults, suggesting that their attempt originates from a more isolated crisis.

Dose-titration effects of fish oil in osteoarthritic dogs.

BACKGROUND: Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). OBJECTIVE: Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. ANIMALS: One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. METHODS: Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. RESULTS: Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. CONCLUSIONS AND CLINICAL IMPORTANCE: Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.

Fear conditioning to discontinuous auditory cues requires perirhinal cortical function.

Pretraining lesions of rat perirhinal (PR) cortex impair fear conditioning to ultrasonic vocalizations (USVs) but have no effect on conditioning to continuous tones. This study attempted to deconstruct USVs into simpler stimulus features that cause fear conditioning to be PR-dependent. Rats were conditioned to one of three cues: a multicall 19-kHz USV, a 19-kHz discontinuous tone, and a 19-kHz continuous tone. The discontinuous tone duplicated the on/off pattern of the individual calls in the USV, but it lacked the characteristic frequency modulations. Well-localized neurotoxic PR lesions impaired conditioning to the USV, the discontinuous tone, and the training context. However, PR lesions had no effect on conditioning to the continuous tone. The authors suggest that the lesion effects on fear conditioning to both cues and contexts reflect the essential role of PR in binding stimulus elements together into unitary representations.

Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata.

BACKGROUND: Chondrodysplasia punctata is a rare heterogeneous group of bone dysplasias occurring with an incidence of one in 100,000 live births. Prenatal sonographic diagnosis of non-rhizomelic chondrodysplasia punctata (Conradi-Hünermann syndrome) has previously been reported only following detection of overall limb shortening. CASE: Multiple sonographic skeletal findings of premature epiphyseal calcifications, other unusual calcifications, kyphoscoliosis, and asymmetrical limb shortening, typical of non-rhizomelic chondrodysplasia punctata, led to second-trimester prenatal sonographic diagnosis of this condition. CONCLUSION: Second-trimester prenatal sonographic diagnosis of premature epiphyseal calcifications associated with non-rhizomelic chondrodysplasia punctata is possible.

The effect of combined therapy with captopril, furosemide, and a sodium-restricted diet on serum electrolyte concentrations and renal function in normal dogs and dogs with congestive heart failure.

Captopril, furosemide, and a sodium-restricted diet were administered to 6 normal dogs and 10 dogs with congestive heart failure. Serum electrolyte concentrations and renal function were monitored in both groups. In the normal dogs, no clinically meaningful changes in serum electrolyte, urea nitrogen, or creatinine concentrations developed during therapy with a sodium-restricted diet and 4 weeks each of furosemide alone, captopril alone, or furosemide plus captopril. Three of 6 normal dogs on furosemide and a sodium-restricted diet had at least one serum potassium concentration above the reference range during the 4 weeks of observation. One normal dog on captopril, furosemide, and a sodium-restricted diet developed azotemia, and 2 dogs had serum potassium concentrations above the reference range during the 4 weeks of observation. Ten dogs with congestive heart failure were treated with captopril, furosemide, a sodium-restricted diet, and digoxin. Etiopathogenesis of the heart failure included valvular insufficiency (n = 6), dilated cardiomyopathy (n = 3), and dilated cardiomyopathy and dirofilariasis (n = 1). Serum electrolyte concentrations and renal function were monitored for 5 consecutive weeks in 7 of the 10 dogs and for 17 weeks or longer in 6. Two dogs were euthanized after 4 weeks because of acute decompensation of heart failure, and one dog developed severe azotemia and uremia. Six of 10 dogs with congestive heart failure had at least one serum potassium concentration above the reference range sometime during the 5 weeks of observation, although the changes in the mean serum potassium concentrations were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of quantitative enzymuria in dogs with gentamicin-induced nephrotoxicosis using urine enzyme/creatinine ratios from spot urine samples.

The correlation between 24-hour urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) with urine NAG and GGT/creatinine ratios was assessed in dogs with gentamicin-induced nephrotoxicosis. Eighteen 6-month-old male Beagles with normal renal function were randomly divided into 3 groups of 6. Each group was fed a different concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued on its respective diet. Endogenous creatinine clearance and 24-hour urinary excretion of NAG and GGT were determined after dietary conditioning (day 0) and on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and GGT/creatinine ratios (IU/L divided by mg/dL) were determined from catheterized spot urine samples obtained between 7 and 10 AM on the same days. The correlation between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the spot urine samples was evaluated by simple linear regression analysis. Spot sample urine enzyme/creatinine ratios were significantly correlated with 24-hour urinary enzyme excretion through day 4 for dogs on low dietary protein, through day 6 for those on medium protein, and through day 8 for those on high dietary protein. Mean +/- SD baseline values for urine NAG/creatinine ratio and 24-hour urinary NAG excretion were 0.06 +/- 0.04 and 0.19 +/- 0.14 IU/kg/24 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Single-injection method for evaluation of renal function with 14C-inulin and 3H-tetraethylammonium bromide in dogs and cats.

A double-isotope single-injection method without urine collection for the estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in dogs and cats was evaluated. The GFR was determined, using 14C-inulin and ERPF was determined, using [3H]tetraethylammonium bromide. Using a modified single exponential, 1-compartment mathematical model, the renal clearance of these solutes was estimated with a plasma radioactivity disappearance curve constructed from samples collected over a 150-minute time period. In 25 dogs, GFR, ERPF, and filtration fraction were 3.55 +/- 0.14 ml/kg/min, 10.51 +/- 0.72 ml/kg/min, and 0.34 +/- 0.02, respectively. In 25 cats, GFR, ERPF, and filtration fraction were 3.24 +/- 0.14 ml/kg/min, 8.14 +/- 0.53 ml/kg/min, and 0.39 +/- 0.02, respectively. This time-efficient and reliable method, using beta-emitting isotopes, yielded renal functional values well within the normal ranges reported by a variety of other isotopic and nonisotopic procedures. The advantages of the present procedure over previous double-isotope single-injection methods include the use of less costly, lower energy-using, and less penetrating beta emittors, as well as a shortened blood sampling schedule.

Renal functional relationships in dogs with glomerulopathies.

Glomerular filtration rate, effective renal plasma flow, and filtration fraction were determined by measuring plasma disappearance of [14C] inulin and [3H]tetraethylammonium bromide after a single IV bolus injection was given to 8 dogs with membranous nephropathy, renal glomerulosclerosis, or renal amyloidosis. Glomerular filtration rate was decreased in the 8 dogs. Effective renal plasma flow was within reference values in 1 dog, increased in 1 dog, and decreased in 6 dogs. Filtration fraction was within reference values in 2 dogs and decreased in 6 dogs. The glomerular filtration rate also was estimated by the endogenous creatinine clearance technique and was decreased in the 8 dogs with glomerulopathies.

Serum concentrations of thyroxine, 3,5,3'-triiodothyronine, thyrotropin, and prolactin in dogs before and after thyrotropin-releasing hormone administration.

Serum concentrations of thyrotropin (TSH), prolactin, thyroxine, and 3,5,3'-triiodothyronine in 15 euthyroid dogs and 5 thyroidectomized and propylthiouracil-treated dogs after thyrotropin-releasing hormone (TRH) administration were measured. Although thyroidectomized and propylthiouracil-treated dogs had higher (P less than 0.01) base-line concentrations of TSH in serum than did euthyroid dogs, concentrations of TSH after TRH administration varied at 7.5, 15, and 30 minutes with 14 of 45 samples obtained from healthy dogs having lower TSH concentrations than before TRH challenge. Similarly, concentrations of 3,5,3'-triiodothyronine in the serum of euthyroid dogs 4 hours after TRH administration were similar (P less than 0.05) to concentrations before TRH challenge. Although the mean concentration of thyroxine in serum was elevated (P less than 0.05) 4 hours after administration of TRH to euthyroid animals, as compared with base-line levels, the individual response was variable with concentrations not changing or decreasing in 4 dogs. Therefore, the TRH challenge test as performed in the current investigation was of limited value in evaluating canine pituitary gland function. Although mean concentrations of TSH in serum were higher (P less than 0.05) in euthyroid dogs after TRH administration, the response was too variable among individual animals for accurate evaluation of pituitary gland function. Concentrations of prolactin in the sera of dogs after TRH administration, confirmed previous reports that exogenously administered TRH results in prolactin release from the canine pituitary and indicated that the TRH used was biologically potent.

Serum concentrations of thyroxine and 3,5,3'-triiodothyronine before and after intravenous or intramuscular thyrotropin administration in dogs.

Response to thyrotropin (TSH) was evaluated in 2 groups of mixed-breed dogs. Thyrotropin (5 IU) was administered IV to dogs in group 1 (n = 15) and IM to dogs in group 2 (n = 15). Venous blood samples were collected immediately before administration of TSH and at 2-hour intervals for 12 hours thereafter. In group 1, the maximum mean concentration (+/- SD) of thyroxine (T4; 7.76 +/- 2.60 micrograms/dl) and 3,5,3'-triiodothyroxine (T3; 1.56 +/- 0.51 ng/ml) was attained at postinjection hours (PIH) 8 and 6, respectively. However, the mean concentration of T4 at PIH 6 (7.21 +/- 2.39 micrograms/dl) was not different (P greater than 0.05) from the mean concentration at PIH 8. The maximum mean concentration of T4 (10.10 +/- 3.50 micrograms/dl) and T3 (2.22 +/- 1.24 ng/ml) in group 2 was attained at PIH 12 and 10, respectively. Because dogs given TSH by the IM route manifested pain during injection, had variable serum concentrations of T3 after TSH administration, and may require 5 IU to achieve maximal increases in serum T4 concentrations, IV administration of TSH is recommended. The optimal sampling time to observe maximal increases in T3 and T4 after IV administration of TSH was 6 hours. Repeat IV administration of TSH may cause anaphylaxis and, therefore, is not recommended.

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of four diets containing approximately 11% protein (dry weight) on uric acid, sodium urate, and ammonium urate urine activity product ratios of healthy beagles.

Urine activity product ratios of uric acid (APRua), sodium urate (APRna), and ammonium urate (APRau), and urinary excretion of 10 metabolites were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of 4 diets containing approximately 11% protein (dry weight) and various protein sources: a 72% moisture, casein-based diet; a 10% moisture, egg-based diet; a 72% moisture, chicken-based diet; and a 71% moisture, chicken-based, liver-flavored diet. Significantly (P < 0.05) higher APRua, APRna, and APRau were observed when dogs consumed the egg-based diet, compared with the other 3 diets; there were no differences in these ratios among the other 3 diets. Twenty-four-hour urinary excretions of chloride, potassium, phosphorus, and oxalic acid were significantly (P < 0.05) higher when dogs consumed the egg-based diet. Twenty-four-hour urinary excretions of sodium were significantly (P < 0.05) higher when dogs consumed the egg-based diet, compared with the casein-based diet and the chicken-based, liver-flavored diet, but were not significantly different between the egg-based diet and chicken-based diet. Twenty-four-hour urine volume was similar when dogs consumed the 4 diets. Twenty-four-hour endogenous creatinine clearance was significantly (P < 0.05) lower when dogs consumed the casein-based diet; there were no differences among the other 3 diets. Although consumption of all diets was associated with production of alkaline urine, the 24-hour urine pH was significantly (P < 0.05) higher when dogs consumed the egg-based diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of two amounts of dietary casein on uric acid, sodium urate, and ammonium urate urinary activity product ratios of healthy beagles.

Casein has been used as a protein source in diets designed to dissolve canine ammonium urate uroliths and to prevent their recurrence, because it contains fewer purine precursors than do many other sources of protein. However, an important question is whether reduced quantities of dietary casein have any benefit in modifying saturation of urine with urates. To answer this question, activity product ratios of uric acid, sodium urate, and ammonium urate were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of consumption of a 10.4% protein, casein-based (10.4% casein) diet and a 20.8% protein, casein-based (20.8%casein) diet. Significantly lower 24-hour urinary excretions of ammonia and phosphorus were observed when dogs consumed the 10.4% casein diet. These results suggest that use of the 10.4% casein diet in protocols designed for dissolution and prevention of uric acid, sodium urate, and ammonium urate uroliths in dogs may be beneficial.

Diet effect on activity product ratios of uric acid, sodium urate, and ammonium urate in urine formed by healthy beagles.

Urine activity product ratios of uric acid, sodium urate, and ammonium urate and urinary excretion of metabolites were determined in 24-hour samples produced by 6 healthy Beagles during periods of consumption of a low-protein, casein-based diet (diet A) and a high-protein, meat-based diet (diet B). Comparison of effects of diet A with those of diet B revealed: significantly lower activity product ratios of uric acid (P = 0.025), sodium urate (P = 0.045), and ammonium urate (P = 0.0045); significantly lower 24-hour urinary excretion of uric acid (P = 0.002), ammonia (P = 0.0002), sodium (P = 0.01), calcium (P = 0.005), phosphorus (P = 0.0003), magnesium (P = 0.01), and oxalic acid (P = 0.004); significantly (P = 0.0001) higher 24-hour urine pH; and significantly (P = 0.01) lower endogenous creatinine clearance. These results suggest that consumption of diet A minimizes changes in urine that predispose dogs to uric acid, sodium urate, and ammonium urate urolithiasis.

Applicability of leukocyte esterase test strip in detection of canine pyuria.

A commercially available leukocyte esterase assay was evaluated for application in analyzing canine urine for the detection of pyuria. In 229 urine samples, the leukocyte esterase activity was compared with leukocyte concentrations, as assessed by microscopic sediment analysis and chamber cell counts. The leukocyte esterase assay was specific (93.2%) for canine pyuria, but was poorly sensitive (46.0%) and did not appear to be applicable to analysis of canine urine samples.

Microbiologic evaluation of canine urine: direct microscopic examination and preservation of specimen quality for culture.

Urine specimens were obtained from 115 dogs. Each specimen was divided into 2 aliquots; one aliquot was placed into a sterile container (non-preserved), and the other was preserved in a boric acid-glycerol-sodium formate at 4 C. Both aliquots were then transported to a laboratory, and specimens of each aliquot were bacteriologically cultured immediately upon arrival at the laboratory. Specimens of the preserved aliquot also were cultured after 24, 48, and 72 hours of preservation. In 47 specimens containing greater than or equal to 1 X 10(4) colony-forming units (CFU)/ml, the results of quantitative bacteriologic culturing of preserved urine at 0, 24, 48, and 72 hours were the same as the result of the immediate quantitative bacteriologic culture of non-preserved urine. In 2 of 5 specimens containing greater than or equal to 1 X 10(3) CFU/ml but less than 1 X 10(4) CFU/ml, the results of quantitative bacteriologic culture of preserved urine differed from the corresponding immediate culture of nonpreserved urine. Bacteria were not isolated from 63 specimens (less than 1 X 10(3) CFU/ml). Bacteriologic cultures of preserved urine were also negative for bacterial growth at 0, 24, 48, and 72 hours. Bacteriuria was detected by direct microscopic examination of gram-stained smears of uncentrifuged urine in 50 of 52 urine specimens from dogs with urinary tract infection. Bacteria were observed in 1 of 63 specimens that did not have bacterial growth when cultured.

Comparison of renal biopsy techniques in dogs.

To evaluate adequacy of biopsy specimens obtained and safety to the patient, the standard keyhole biopsy technique (using digital immobilization of the right kidney and placement of the biopsy needle up to the capsule before obtaining a tissue sample) was compared with 9 technical modifications. Adequacy was judged by the number of intact glomeruli observed in the specimen. Detection of transected blood vessels and renal pelvis was presumed to have predictive value for postbiopsy complications of hemorrhage and hydronephrosis. Needle biopsy specimens were also obtained from left and right kidneys by use of laparoscopic visualization and were compared with those obtained by use of the standard keyhole technique. Although the standard keyhole technique yielded the highest percentage of adequate biopsy specimens, there was no statistical difference between specimens obtained by this technique and those obtained by the modified technique or by laparoscope-guided biopsy. Also, significant difference in percentage of biopsy specimens with renal pelvis was not found between specimens obtained by the standard and modified techniques. For each technique, the biopsy core length was measured and the mean value was calculated. In this study, core length did not correlate with adequacy of the biopsy specimen.

Hyperammonemia associated with urethral obstruction in a dog.

Hyperammonemia was documented in a 10-week-old male Lhasa Apso referred for urethral obstruction and rupture. Results of liver function tests were normal. Staphylococcus sp was isolated from urine. Anomalies of the portal vascular system and hepatic insufficiency are the most common causes of hyperammonemia in the dog. Hyperammonemia, however, in the absence of recognizable concurrent hepatic disease, also may result from urinary stasis and infection with urea-splitting organisms.