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.

Species-specific injury-induced cell proliferation in the hippocampus and subventricular zone of food-storing and nonstoring wild birds.

Cells are continuously born and incorporated into the adult hippocampus (HP). Adult neurogenesis might act to increase the total number of cells or replace dead cells. Thus, neurogenesis might be a primary factor in augmenting, maintaining, or even recovering functions. In zebra finches, HP injury increases cell proliferation in the HP and stem cell rich subventricular zone (SVZ). It is unknown what effect injury has on a species dependent upon the HP for survival in the wild. In food-storing birds, recovery of caches is seasonal, necessary for survival, dependent upon the HP and is concomitant with a peak in HP neurogenesis. During the fall, food-storing black-capped chickadees (BCCs) and nonstoring dark-eyed juncos (DEJs) were captured and given a unilateral penetrating lesion to the HP one day later. On day 3, birds were injected with the mitotic marker 5-bromo-2'-deoxyuridine (BrdU) and perfused on day 10. If unlesioned, more BrdU-labeled cells were observed in the HP and SVZ of BCCs compared to DEJs, indicating higher innate cell proliferation or incorporation in BCCs. If lesioned, BrdU-labeled cells increased in the injured HP of both species; however, lesions caused larger increases in DEJs. DEJs also showed increases in BrdU-labeled cells in the SVZ and contralateral HP. BCCs showed no such increases on day 10. Thus, during the fall food-storing season, storers showed suppressed injury-induced cell proliferation and/or reduced survival rates of these new cells compared to nonstorers. These species differences may provide a useful model for isolating factors involved in cellular responses following injury.

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.

Effects of hydrochlorothiazide and diet in dogs with calcium oxalate urolithiasis.

OBJECTIVE: To determine whether hydrochlorothiazide (HCTZ) reduces urinary calcium excretion in dogs with calcium oxalate urolithiasis. DESIGN: Original study. ANIMALS: 8 dogs with calcium oxalate urolithiasis. PROCEDURE: 4 treatment protocols were evaluated in each dog (a low calcium, low protein diet designed to prevent calcium oxalate urolith formation with and without administration of HCTZ [2 mg/kg (0.9 mg/lb) of body weight, PO, q 12 h] and a maintenance diet with higher quantities of protein and calcium with and without administration of HCTZ). At the end of each 2-week treatment period, 24-hour urine samples were collected. Blood samples were collected during the midpoint of each urine collection period. Analysis of variance was performed to evaluate the effects of HCTZ and diet on urine and serum analytes. RESULTS: Hydrochlorothiazide significantly decreased urine calcium and potassium concentration and excretion. Hydrochlorothiazide also significantly decreased serum potassium concentration. Compared with the maintenance diet, the urolith prevention diet significantly decreased urine calcium and oxalic acid concentration and excretion. Dogs consuming the urolith prevention diet had significantly lower serum concentrations of albumin and urea nitrogen. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of HCTZ decreased urine calcium excretion in dogs with a history of calcium oxalate urolith formation. The greatest reduction in urine calcium concentration and excretion was achieved when dogs received HCTZ and the urolith prevention diet. Results of this study suggest that the hypocalciuric effect of HCTZ will minimize recurrence of calcium oxalate urolith formation in dogs; however, long-term controlled clinical trials are needed to confirm the safety and effectiveness of HCTZ.

Patient and environmental factors associated with calcium oxalate urolithiasis in dogs.

OBJECTIVE: To test the hypothesis that breed, age, sex, body condition, and environment are risk factors for development of calcium oxalate uroliths in dogs. DESIGN: Case-control study. ANIMALS: 1,074 dogs that formed calcium oxalate uroliths and 1,724 control dogs that did not have uroliths. PROCEDURE: A validated multiple-choice questionnaire was designed to collect information from veterinarians and owners within 1 year of the date of urolith detection concerning signalment and environment of the dogs. Univariate and multivariate analyses were performed to calculate odds ratios to assess whether breed, age, sex, body condition, and environment were risk factors for calcium oxalate urolith formation. RESULTS: Middle-aged (8- to 12-year-old) castrated male dogs had increased risk for formation of calcium oxalate uroliths. Urolith formation was also associated with increasing age. Dogs of certain breeds, including Miniature and Standard Schnauzer, Lhasa Apso, Yorkshire Terrier, Bichon Frise, Shih Tzu, and Miniature and Toy Poodle, had increased risk for developing calcium oxalate uroliths. Overweight dogs also had increased risk. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of patient and environmental risk factors for development of calcium oxalate uroliths may facilitate development of surveillance strategies that result in earlier detection of this disease. Modification of environmental factors and body weight may minimize calcium oxalate urolith formation and recurrence.

Methods for evaluating treatment of uroliths.

Formation of uroliths is not a disease but rather a complication of several disorders. Some disorders can be identified and corrected (e.g., infection-induced struvite urolith formation), and some can be identified but not corrected (e.g., hyperuricosuria occurring in Dalmatians that form ammonium urate uroliths), although for others, the underlying etiopathogenesis is not known (e.g., calcium oxalate urolith formation in Miniature Schnauzers). A common denominator of these disorders is that from time to time, they can create oversaturation of urine with one or more crystal precursors, resulting in formation of crystals. To develop rational and effective approaches to treatment, abnormalities that promote urolith formation must be identified with the goal of eliminating or modifying them. It is therefore important to understand several basic concepts associated with urolithiasis.

Medical dissolution and prevention of canine struvite urolithiasis. Twenty years of experience.

Two types of canine struvite uroliths have been recognized: infection-induced struvite is the most common type; sterile struvite is uncommonly recognized. Infection-induced struvite is most commonly associated with urease-producing staphylococcal UTI. For dogs that qualify, medical dissolution is an effective method of treatment. Medical dissolution protocols encompass: (1) eradication or control of UTI; (2) use of calculolytic diets; and (3) administration of urease inhibitors to patients with persistent UTI caused by urease-producing microbes.

Canine calcium oxalate urolithiasis. Case-based applications of therapeutic principles.

The case study presented here illustrates the diagnosis and management of calcium oxalate urolithiasis in a Bichon Frise, a breed at increased risk for this type of stone. If the Bichon Frise had persistent hypercalcemia, we would have evaluated serum concentrations of ionized calcium, parathyroid hormone, and vitamin D to identify an underlying cause. Because his urine was alkaline, additional potassium citrate was not provided. Likewise, as a fortified diet was fed to him, vitamin B6 therapy was not considered. This case study illustrates the benefits of radiographic evaluation immediately following surgery and during follow-up examinations. If we had postponed radiographs until the patient developed clinical signs, additional surgical procedures may have been required.

Measurement of the influence of diet on feline urinary pH.

The kidneys eliminate the acid produced each day by metabolism and diet. Consequently, urinary pH is influenced by diet. The urinary pH of cats consuming a natural habitual diet consisting of small mammal carcasses is between 6.2 and 6.4. Although the only authoritative way to determine the effect of diet on urinary pH is a feeding trial, there is no universally accepted protocol for measuring urinary pH. When interpreting the urinary pH of a spot or random sample, it is necessary to consider when the sample was obtained relative to time of eating.

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)

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.

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)

Prenatal diagnosis of moderate unilateral hydrocephalus subsequently not requiring neonatal decompression.

Prenatal diagnosis of unilateral hydrocephalus is unusual. In the past most such cases have been treated with neonatal shunting procedures. We present an unusual case in which moderate unilateral hydrocephalus was diagnosed prenatally at 30 weeks' gestation. Despite prenatal and neonatal sonographic signs of both cortical thinning and mild displacement of midline intracranial structures, confirmed by computed tomography, neonatal shunting was not required. The findings and course in this unusual case suggest that infrequently some of the milder cases of idiopathic nonprogressive unilateral hydrocephalus discovered later in life may possibly represent late detection of this preexisting condition.

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)