Category Archives: research

Scientists test nanoparticle drug delivery in dogs with osteosarcoma

At the University of Illinois, an engineer teamed up with a veterinarian to test a bone cancer drug delivery system in animals bigger than the standard animal model, the mouse. They chose dogs – mammals closer in size and biology to humans – with naturally occurring bone cancers, which also are a lot like human bone tumors.

wikimedia-commons-photo-of-bmd

Dogs with naturally occurring cancers are more similar in size and biology to humans than are other mammals, such as mice. Public domain photo: Wikimedia Commons

In clinical trials, the dogs tolerated the highest planned doses of cancer-drug-laden nanoparticles with no signs of toxicity. As in mice, the particles homed in on tumor sites, thanks to a coating of the drug pamidronate, which preferentially binds to degraded sites in bone. The nanoparticles also showed anti-cancer activity in mice and dogs.

The researchers report their results in the Proceedings of the National Academy of Sciences.

These findings are a proof-of-concept that nanoparticles can be used to target bone cancers in large mammals, the researchers said. The approach may one day be used to treat metastatic skeletal cancers, they said.

The dogs were companion animals with bone cancer that were submitted for the research trials by their owners, said U. of I.  Professor Dr Timothy Fan, who led the study with materials science and engineering Professor Jianjun Cheng.  All of the dogs were 40 to 60 kilograms (88 to 132 pounds) in weight, he said.

“We wanted to see if we could evaluate these drug-delivery strategies, not only in a mouse model, but also at a scale that would mimic what a person would get,” Fan said. “The amount of nanoparticle that we ended up giving to these dogs was a thousand-fold greater in quantity than what we would typically give a mouse.”

Using nanoparticles with payloads of drugs to target specific tissues in the body is nothing new, Cheng said. Countless studies test such approaches in mice, and dozens of “nanopharmaceuticals” are approved for use in humans. But the drug-development pipeline is long, and the leap from mouse models to humans is problematic, he said.

“Human bone tumors are much bigger than those of mice,” Cheng said. “Nanoparticles must penetrate more deeply into larger tumors to be effective. That is why we must find animal models that are closer in scale to those of humans.”

Mice used in cancer research have other limitations. Researchers usually inject human or other tumor cells into their bodies to mimic human cancers, Fan said. They also are bred to have compromised immune systems, to prevent them from rejecting the tumors.

“That is one of the very clear drawbacks of using a mouse model,” Fan said. “it doesn’t recapitulate the normal immune system that we deal with every day in the person or in a dog.”

There also are limitations to working with dogs, he said. Dogs diagnosed with bone cancer often arrive at the clinic at a very advanced stage of the disease, whereas in humans, bone cancer is usually detected early because people complain about the pain and have it investigated.

“On the flip side of that, I would say that if you are able to demonstrate anti-cancer activity in a dog with very advanced disease, then it would be likely that you would have equivalent or better activity in people with a less advanced stage of the disease,” Fan said.

Many more years of work remain before this or a similar drug-delivery system can be tested in humans with inoperable bone cancer, the researchers said.

Source:  Illinois News Bureau media release

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Children are unaware of the risks of approaching frightened dogs

Children understand the risks of approaching an angry dog but they are unaware that they should show the same caution around frightened dogs says a study presented to the British Psychological Society’s Developmental Psychology Section’s annual conference this week.

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Lead researcher Dr Sarah Rose of Staffordshire University said: “UK statistics show that young children are at the highest risk of being bitten by a dog with nearly 1200 admissions to hospital for under 10’s during 2013-2014. This study explored whether the explanation is that they are unable to accurately recognise a dog’s emotions when approaching one.”

Dr Rose and Grace Alridge (also of Staffordshire University) asked two groups of children aged 4 to 5 (57) and 6 to 7 years old (61) to watch 15 videos and look at 15 images showing real life behaviour of dogs.  Video clips were all between 6 and 11 seconds long and the only auditory information was the dog barking. The images and videos used had been watched by two veterinary nurses and two laypeople who had agreed on the emotion the dog was showing.

Both groups were asked questions relating to their intention to approach the dog (Would you play with this dog?) and what emotion they thought the dog was experiencing (How happy/angry/frightened do you think this dog is feeling?).

Analysis of the results showed that the children recognised happy, angry and frightened dogs in videos and images at above the level of chance. Furthermore, they recognised angry dogs more accurately than happy or frightened dogs.

However, although the children were less likely to approach an angry dog there was no difference in their inclination to approach a happy or frightened dog.

Dr Rose said: “Young children are relatively good at accurately identifying the emotion that a dog is displaying. However, children’s understanding of safety around dogs is lacking as they only demonstrated caution about approaching angry dogs. They appeared to be unaware that there might be problems approaching frightened dogs. This finding should help inform dog bite prevention campaigns.” 

Source:  The British Psychological Society media release

Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Praise or food?

Given the choice, many dogs prefer praise from their owners over food, suggests a new study published in the journal Social, Cognitive and Affective Neuroscience. The study is one of the first to combine brain-imaging data with behavioral experiments to explore canine reward preferences.

“We are trying to understand the basis of the dog-human bond and whether it’s mainly about food, or about the relationship itself,” says Gregory Berns, a neuroscientist at Emory University and lead author of the research. “Out of the 13 dogs that completed the study, we found that most of them either preferred praise from their owners over food, or they appeared to like both equally. Only two of the dogs were real chowhounds, showing a strong preference for the food.”

food-or-praise

Praise Pooch: Most of the dogs in the experiments preferred praise over food, or liked them both equally. Kady, a Labrador-golden retriever mix, was the top dog when it came to the strength of her preference for praise.

Dogs were at the center of the most famous experiments of classical conditioning, conducted by Ivan Pavlov in the early 1900s. Pavlov showed that if dogs are trained to associate a particular stimulus with food, the animals salivate in the mere presence of the stimulus, in anticipation of the food.

“One theory about dogs is that they are primarily Pavlovian machines: They just want food and their owners are simply the means to get it,” Berns says. “Another, more current, view of their behavior is that dogs value human contact in and of itself.”

Berns heads up the Dog Project in Emory’s Department of Psychology, which is researching evolutionary questions surrounding man’s best, and oldest friend. The project was the first to train dogs to voluntarily enter a functional magnetic resonance imaging (fMRI) scanner and remain motionless during scanning, without restraint or sedation. In previous research, the Dog Project identified the ventral caudate region of the canine brain as a reward center. It also showed how that region of a dog’s brain responds more strongly to the scents of familiar humans than to the scents of other humans, or even to those of familiar dogs.

chowhound

Chowhound: Ozzie, a shorthaired terrier mix, was the only dog in the experiments that chose food over his owner’s praise 100 percent of the time. “Ozzie was a bit of an outlier,” Berns says, “but Ozzie’s owner understands him and still loves him.”

For the current experiment, the researchers began by training the dogs to associate three different objects with different outcomes. A pink toy truck signaled a food reward; a blue toy knight signaled verbal praise from the owner; and a hairbrush signaled no reward, to serve as a control.
The dogs then were tested on the three objects while in an fMRI machine. Each dog underwent 32 trials for each of the three objects as their neural activity was recorded.

All of the dogs showed a stronger neural activation for the reward stimuli compared to the stimulus that signaled no reward, and their responses covered a broad range. Four of the dogs showed a particularly strong activation for the stimulus that signaled praise from their owners. Nine of the dogs showed similar neural activation for both the praise stimulus and the food stimulus. And two of the dogs consistently showed more activation when shown the stimulus for food.

The dogs then underwent a behavioral experiment. Each dog was familiarized with a room that contained a simple Y-shaped maze constructed from baby gates: One path of the maze led to a bowl of food and the other path to the dog’s owner. The owners sat with their backs toward their dogs. The dog was then repeatedly released into the room and allowed to choose one of the paths. If they came to the owner, the owner praised them.

“We found that the caudate response of each dog in the first experiment correlated with their choices in the second experiment,” Berns says. “Dogs are individuals and their neurological profiles fit the behavioral choices they make. Most of the dogs alternated between food and owner, but the dogs with the strongest neural response to praise chose to go to their owners 80 to 90 percent of the time. It shows the importance of social reward and praise to dogs. It may be analogous to how we humans feel when someone praises us.”

The experiments lay the groundwork for asking more complicated questions about the canine experience of the world. The Berns’ lab is currently exploring the ability of dogs to process and understand human language.

“Dogs are hypersocial with humans,” Berns says, “and their integration into human ecology makes dogs a unique model for studying cross-species social bonding.”

Source:  Emory University media release

Pet therapy can combat homesickness

The expression dog is man’s best friend might have more weight in the case of first-year university students suffering from homesickness, according to a new UBC study.

The study shows that animal-assisted therapy can help students combat homesickness and could be a useful tool in lowering post-secondary drop-out rates.

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John Tyler Binfet, seen with his dog Frances, conducted a study on the effect of pet therapy on homesickness. Binfet runs the Building Academic Retention Through K’9s (B.A.R.K.) program at UBC’s Okanagan campus. Credit: UBC

“Transitioning from high school to university can prove to be a challenge for many first-year students,” says Assistant Professor John Tyler Binfet of UBC’s Okanagan campus.

“Given that students who experience homesickness are more likely than their non-homesick cohorts to drop out of university, universities have a vested interest in supporting students during their first-year transition.”

In the study, 44 first-year university students who self-identified as homesick were given a survey to measure levels of homesickness, satisfaction with life and connectedness with campus. Half of the students completed eight weeks of dog therapy, while the other half were informed that their sessions would begin in eight weeks’ time. Dog therapy included 45-minute weekly sessions involving small group interactions with the dogs and handlers, and engagement with other first-year students participating in the study.

Following the initial eight-week session, participants in both the treatment group and the non-treatment group completed the survey again.

Participants who completed the eight-week program experienced significant reductions in homesickness and greater increase in satisfaction with life. Participants reported that sessions “felt like they were at home chatting with friends who brought their puppies.” While the non-treatment group reported an increase in their feelings of homesickness.

According to a 2009 report conducted for B.C. Stats, students who left post-secondary happy were almost twice as likely to have felt a sense of belonging compared to students who left unhappy. Students who left university unhappy were almost twice as likely to say they did not feel a sense of belonging on campus.

A total of 29 per cent of students who dropped out cited more interactions and friendships with other students as a factor that would have influenced their decision to stay longer.

While further study is needed, a university’s ability to influence campus connections could be a useful tool in lowering drop-out rates in first-year students, says Binfet.

“Many first-year university students face the challenge of integrating into their new campus community,” says Binfet. “Homesick students are three times more likely than those who manage their homesickness to disengage and drop out of university.”

“Moving to a new city, I did not know anyone at the university and became very homesick and depressed,” says UBC Okanagan student Varenka Kim. “I was mainly secluded in my dorm room and did not feel like I belonged here. Coming to animal assisted therapy sessions every Friday gave me a sense of purpose and kept me enthusiastic about life.”

Source:  University of British Columbia media release

Gambling wolves take more risks than dogs

Would you rather get 100 euros for certain, or have a fifty-fifty chance of receiving either 200 euros or nothing? Most choose the first, as humans tend to be “risk-averse”, preferring a guaranteed pay-off over the possibility of a greater reward. It is thought that the human preference for “playing it safe” has evolved through natural selection: when you live precariously, like our remote ancestors, losing all your food reserves might be catastrophic, while adding to them might not make much difference to your chances of survival.

Wolf pups

Etu and Ela, two wolf pups at the Wolf Centre Photo credit: Rooobert Bayer

Here, in one of the first studies on risk preferences in animals other than primates, scientists show that wolves are consistently more prone to take risks when gambling for food than dogs. When faced with the choice between an insipid food pellet and a fifty-fifty chance of either tasty meat or an inedible stone, wolves nearly always choose the risky option, whereas dogs are more cautious.

“We compared the propensity to take risks in a foraging context between wolves and dogs that had been raised under the same conditions,” says Sarah Marshall-Pescini, a postdoctoral fellow at the Messerli Research Institute at the Veterinary University of Vienna and the Wolf Science Centre, Ernstbrunn, Austria, the study’s first author. “We found that wolves prefer the risky option significantly more often than dogs. This difference, which seems to be innate, is consistent with the hypothesis that risk preference evolves as a function of ecology.”

The study was done at the Wolf Science Centre, Ernstbrunn, Austria, a research institute where scientists study cognitive and behavioral differences and similarities between wolves and dogs. Here, wolves and dogs live in packs, under near-natural conditions within large enclosures.

Marshall-Pescini let each of 7 wolves and 7 dogs choose 80 times between two upside-down bowls, placed side-by-side on a movable table-top. The animals had been trained to indicate the bowl of their choice with their paw or muzzle, after which they would receive the item that was hidden beneath it.

The researchers had taught the wolves and dogs that beneath the first bowl, the “safe” option, was invariably an insipid food pellet, while beneath the second bowl, the “risky” option, was either an inedible item, a stone, in a random 50% of trials, and high-quality food, such as meat, sausage, or chicken, in the other 50%. As a control, the side for the “safe” and “risky” option changed between trials, but the animals were always shown which side corresponded to which option; whether they would get a stone or high-quality food if they chose the “risky” option was the only unknown. Rigorously designed control trials confirmed that the animals understood this rule, including the element of chance.

Wolves are much more prone to take risks than dogs, show the results. Wolves chose the risky option in 80% of trials, whereas dogs only did so in 58% of trials.

The researchers believe that dogs evolved a more cautious temperament after they underwent an evolutionary shift from their ancestral hunter lifestyle to their present scavenger lifestyle, which happened between 18,000 to 32,000 years ago when humans first domesticated dogs from wolves. Previous research has suggested that species that rely on patchily distributed, uncertain food sources are generally more risk-prone. For example, chimpanzees, which feed on fruit trees and hunt for monkeys, are more risk-prone than bonobos, which rely more on terrestrial vegetation, a temporally and spatially reliable food source.

“Wild wolves hunt large ungulates — a risky strategy, not only because hunts often fail, but also because these prey animals can be dangerous — whereas free-ranging dogs, which make up 80% of the world’s dog population, feed mostly by scavenging on human refuse, a ubiquitous, unlimited resource. So dogs no longer need to take risks when searching for food, and this may have selected for a preference to play if safe,” concludes Marshall-Pescini.

Source:  EurekAlert! media statement

Dogs understand both vocabulary and intonation of human speech

Dogs in MRI machine

Trained dogs are around the fMRI scanner. This material relates to a paper that appeared in the Sept. 2, 2016, issue of Science, published by AAAS. The paper, by A. Andics at Eötvös Loránd University in Budapest, Hungary, and colleagues was titled, “Neural mechanisms for lexical processing in dogs.”  Credit:  Enik Kubinyi

Sometimes research about our dogs goes viral which is the case with this latest research.  It’s already done the rounds on Facebook because it has been reported by several major news agencies.

Here is the original media release  from the American Association for the Advance of Science in its entirety:

Dogs have the ability to distinguish vocabulary words and the intonation of human speech through brain regions similar to those that humans use, a new study reports.

Attila Andics et al. note that vocabulary learning “does not appear to be a uniquely human capacity that follows from the emergence of language, but rather a more ancient function that can be exploited to link arbitrary sound sequences to meanings.” Words are the basic building blocks of human languages, but they are hardly ever found in nonhuman vocal communications. Intonation is another way that information is conveyed through speech, where, for example, praises tend to be conveyed with higher and more varying pitch.

Humans understand speech through both vocabulary and intonation. Here, Andics and colleagues explored whether dogs also depend on both mechanisms. Dogs were exposed to recordings of their trainers’ voices as the trainers spoke to them using multiple combinations of vocabulary and intonation, in both praising and neutral ways. For example, trainers spoke praise words with a praising intonation, praise words with a neutral intonation, neutral words with a praising intonation, and neutral words with neutral intonation.

Researchers used fMRI to analyze the dogs’ brain activity as the animals listened to each combination. Their results reveal that, regardless of intonation, dogs process vocabulary, recognizing each word as distinct, and further, that they do so in a way similar to humans, using the left hemisphere of the brain. Also like humans, the researchers found that dogs process intonation separately from vocabulary, in auditory regions in the right hemisphere of the brain. Lastly, and also like humans, the team found that the dogs relied on both word meaning and intonation when processing the reward value of utterances. Thus, dogs seem to understand both human words and intonation.

The authors note that it is possible that selective forces during domestication could have supported the emergence of the brain structure underlying this capability in dogs, but, such rapid evolution of speech-related hemispheric asymmetries is unlikely. Humans, they say, are only unique in their ability to invent words.

Source:  EurekAlert! media release

Canine hereditary diseases more common than previously indicated

Comment from me (DoggyMom):  I am particularly pleased to read in this media release that the researchers are recommending cooperation between industry, science and laypersons.  As a canine massage therapist, I have found the traditional ‘evidence-based medicine’ fraternity reluctant to involve specialists in other fields and particularly those that are not research scientists or veterinarians.
It is my hope that we can cooperate more in the future as we undertake research into dog health and behavior because by sharing different points of view and expertise, we develop a richer range of options in problem-solving.
Kathleen Crisley, specialist in dog massage, rehabilitation and nutrition/food therapy, The Balanced Dog, Christchurch, New Zealand

Genoscoper Ltd. has published in cooperation with the researchers of University of Helsinki and Pennsylvania (USA) the most comprehensive study on canine hereditary disorders so far. The research brings new information about genetic disorders causing diseases in different dog breeds. The results can be utilized both in dog breeding and veterinary diagnostics. The study was published on PLOS ONE on 15 August 2016.
Dogs have more hereditary diseases than previously thought

Dogs have more hereditary diseases than previously thought. Photo: Eeva Karmitsa

– We noted that surprisingly many canine inherited disorders are actually more widespread than indicated by their original discovery studies, which opens up the door for several future scientific investigations, explains senior author Dr. Hannes Lohi from the University of Helsinki canine genetics research group.

– The technological potential to test a dog for multiple inherited disorders at once has existed for several years. The challenge is to harness that potential for practical use in improved veterinary disease diagnostics, sustainable breeding selections, personalized pet care, and canine genetics research, says lead author Dr. Jonas Donner of Genoscoper Laboratories. Genoscoper Ltd. is a Finnish company specialized in animal genetics and gene testing.

By testing nearly 7000 dogs representing around 230 different breeds for predisposition to almost 100 genetic disorders, the research team observed that 1 in 6 dogs carried at least one of the tested disease predisposing genetic variants in their genome. Moreover, 1 in 6 of the tested genetic variants was also discovered in a dog breed in which it had not previously been reported in the scientific literature. Through clinical follow up of dogs genetically at risk, the research team was able to confirm that several disorders cause the same disease signs also in other than previously described breeds.

– Precisely as we humans, every dog is likely to carry genetic predisposition for some inherited disorder, so we expect these numbers to grow as the numbers of tested disease variants, breeds, and dogs further increase, confirms Dr. Donner.

Co­oper­a­tion is key to health­ier dogs

– Our study demonstrates the importance of collaboration between different contributors – academics, industry and dog fanciers – to reach novel resources that not only enable better understanding of canine genetic health across breeds but also provides viable solutions to improve the health.  The published study provides also an excellent example of the added value of research collaborations between academia and industry in a form that leads to a powerful innovation that start changing the everyday practice in veterinary medicine and improves the welfare of our dogs, says Lohi.

Ge­netic panel screen­ing de­liv­ers res­ults

The study concludes that comprehensive screening for canine inherited disorders represents an efficient and powerful diagnostic and research discovery tool that has a range of applications in veterinary care, disease research, and dog breeding. The authors emphasize that availability of complex DNA-based information is important progress for improvement of the health of purebred dogs, but it should be utilized in combination with other established approaches that promote sustainable breeding and benefit breed health.

The full scientific publication can be accessed here.

Reference:
Donner J, Kaukonen M, Anderson H, Möller F, Kyöstilä K, Sankari S, Hytönen MK, Giger U and Lohi H. Genetic panel screening of nearly 100 mutations reveals new insights into the breed distribution of risk variants for canine hereditary disorders. PlosONE, 1(8): e0161005. doi:10.1371/journal.pone.0161005, 2016.

Source:  University of Helsinki media release