Publisher Health

Researchers have found that a suite of complementary tests can quantify changes in dogs suspected of suffering from cognitive decline. The approach could not only aid owners in managing their elderly canine’s care, but could also serve as a model for evaluating cognitive decline progression in — and treatments for — humans with Alzheimer’s disease.
Canine cognitive dysfunction syndrome (CCDS) is similar to Alzheimer’s disease in humans in that cognitive decline is associated with the development of amyloid plaques as well as cortical atrophy, a progressive degeneration of brain tissue. CCDS is also challenging to diagnose. Traditionally, CCDS is diagnosed based on ruling out any obvious physical conditions and an owner’s answers to a questionnaire.
“One problem with the current approach is that questionnaires only capture a constellation of home behaviors,” says Natasha Olby, the Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at North Carolina State University and co-senior author of a paper describing the work. “There can be other reasons for what an owner may perceive as cognitive decline — anything from an undiagnosed infection to a brain tumor.”
Olby and co-senior author Margaret Gruen, assistant professor of behavioral medicine at NC State, wanted to determine whether cognitive function could be accurately quantified in dogs.
“Our goal was to bring together multiple tools in order to get a more complete picture of how CCDS presents in dogs,” Gruen says.
To that end, the researchers recruited 39 dogs from 15 breeds. All of them were in the senior and geriatric age range, but in good health overall. A dog is considered “senior” if it is in the last 25% of its expected life span based on breed and size, and geriatric beyond that.
The dogs underwent physical and orthopedic exams, as well as lab work that included a blood test that is a marker of neuronal death. Their owners filled out two commonly used diagnostic questionnaires, and then the dogs participated in a series of cognitive tests designed to assess executive function, memory and attention.
“The approach we took isn’t necessarily designed to be diagnostic; instead, we want to use these tools to be able to identify dogs at an early stage and be able to follow them as the disease progresses, quantifying the changes,” Olby says.
The team found that cognitive and blood test results correlated well with the questionnaire scores, suggesting that a multi-dimensional approach can be used to quantify cognitive decline in aging dogs.
“Being able to diagnose and quantify CCDS in a way that is clinically safe and relevant is a good first step toward being able to work with dogs as a model for Alzheimer’s disease in humans,” Olby says. “Many of the current models of Alzheimers disease — in rodents, for example — are good for understanding physiological changes, but not for testing treatments.”
“Dogs live in our homes and develop naturally occurring disease just like we do,” Gruen says. “These findings show promise for both dogs and humans in terms of improving our understanding of disease progression as well as for potentially testing treatments.”
The work appears in the Journal of Alzheimer’s Disease. NC State postdoctoral fellows Gilad Fefer and Wojciech K. Panek are co-first authors of the work.
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Materials provided by North Carolina State University. Original written by Tracey Peake. Note: Content may be edited for style and length.

Immunotherapy unleashes the power of the immune system to fight cancer. However, for some patients, immunotherapy doesn’t work, and new research may help explain why. When immune cells called T lymphocytes infiltrate malignant tumors, the genetic program of those T cells and the developmental path they then follow, may affect their response to immunotherapy and predict overall patient survival, according to a new study by Weill Cornell Medicine investigators. The results overturn the prevailing model of immune responses in melanoma and present different therapeutic approaches.
In the study, published May 9 in Cancer Cell, the investigators analyzed thousands of human tumor samples, plus individual human T cells across many data sets and tumor types, and compared these to many models of T cell behavior in response to infections, cancer and vaccines, including human vaccines. They found that T cells either become stuck in an early activation state or develop into memory cells that are expanded by current immunotherapy approaches.
“The T cells don’t behave in a singular manner, but we can understand their behavior and model it in a way that can predict patient outcomes and overall survival,” said senior author Dr. Niroshana Anandasabapathy, associate professor of dermatology and of dermatology in microbiology and immunology at Weill Cornell Medicine, and a practicing dermatologist for melanoma patients at NewYork-Presbyterian/Weill Cornell Medical Center.
Scientists have long known that the immune system can detect and eliminate tumor cells on its own, but this process sometimes breaks down, leading to the development of cancer. Previous data seemed to support a theory in which, once a tumor is established, T lymphocytes entering the tumor keep seeing and responding to tumor proteins until they become exhausted and unable to attack the cancerous cells. That theory was used to explain the success of a type of therapy called immune checkpoint blockade, which uses cellular signals to improve T cell responses, reawakening the T cells’ ability to attack and eliminate the tumor.
Some patients’ tumors don’t respond to immune checkpoint blockade, though. To figure out why, the team began looking at larger data sets and analyzing them more broadly than previous studies.
“We wanted to take an entirely agnostic approach to trying to understand what happens to a T cell when it enters the tumor microenvironment — a really naive, unbiased approach,” said Dr. Anandasabapathy, who is also a member of the Sandra and Edward Meyer Cancer Center and the Englander Institute for Precision Medicine.
By using large programs of many genetic markers and multiple, simultaneous genomic strategies to categorize cell fates, Dr. Anandasabapathy and her collaborators were able to re-classify T cells in tumors, and better model how they develop. The results show that infiltrating T cells don’t all meet the same fate in every tumor. In contrast to the standard view, a “failure to launch” beyond early activation and convert to memory, and not exhaustion appeared to be the problem. The enrichment of long-lived memory programs correlates strongly with overall survival and a successful response to immune checkpoint blockade therapy in melanoma.
In addition to predicting outcomes, the investigators hope to find ways to change them. Getting T cells past their failure to launch and inducing the formation of tumor-infiltrating memory T cells in patients who lack them, for example, could make non-responsive tumors sensitive to immune checkpoint blockade.
While the current work focused on malignant melanoma, the scientists also identified that similar phenomena likely underlie differences in patient T cell responses to other types of cancer, including kidney, bladder, prostate and liver cancer.
“The power of the study is really in opening new avenues of discovery and suggesting more rational therapeutics,” said first author Abhinav Jaiswal, a doctoral candidate at Weill Cornell Graduate School of Medical Sciences in Dr. Anandasabapathy’s laboratory.
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Materials provided by Weill Cornell Medicine. Note: Content may be edited for style and length.

Imagine being able to measure your blood sugar levels, know if you’ve had too much to drink, and track your muscle fatigue during a workout, all in one small device worn on your skin. Engineers at the University of California San Diego have developed a prototype of such a wearable that can continuously monitor several health stats — glucose, alcohol, and lactate levels — simultaneously in real-time.
The device is about the size of a stack of six quarters. It is applied to the skin through a Velcro-like patch of microscopic needles, or microneedles, that are each about one-fifth the width of a human hair. Wearing the device is not painful — the microneedles barely penetrate the surface of the skin to sense biomolecules in interstitial fluid, which is the fluid surrounding the cells beneath the skin. The device can be worn on the upper arm and sends data wirelessly to a custom smartphone app.
Researchers at the UC San Diego Center for Wearable Sensors describe their device in a paper published May 9 in Nature Biomedical Engineering.
“This is like a complete lab on the skin,” said center director Joseph Wang, a professor of nanoengineering at UC San Diego and co-corresponding author of the paper. “It is capable of continuously measuring multiple biomarkers at the same time, allowing users to monitor their health and wellness as they perform their daily activities.”
Most commercial health monitors, such as continuous glucose monitors for patients with diabetes, only measure one signal. The problem with that, the researchers said, is that it leaves out information that could help people with diabetes, for example, manage their disease more effectively. Monitoring alcohol levels is useful because drinking alcohol can lower glucose levels. Knowing both levels can help people with diabetes prevent their blood sugar from dropping too low after having a drink. Combining information about lactate, which can be monitored during exercise as a biomarker for muscle fatigue, is also useful because physical activity influences the body’s ability to regulate glucose.
“With our wearable, people can see the interplay between their glucose spikes or dips with their diet, exercise and drinking of alcoholic beverages. That could add to their quality of life as well,” said Farshad Tehrani, a nanoengineering Ph.D. student in Wang’s lab and one of the co-first authors of the study.

Young men with a poor diet saw a significant improvement in their symptoms of depression when they switched to a healthy Mediterranean diet, a new study shows.
Depression is a common mental health condition that affects approximately 1 million Australians each year. It is a significant risk factor for suicide, the leading cause of death in young adults.
The 12-week randomised control trial, conducted by researchers from the University of Technology Sydney, was recently published in the peer-reviewed American Journal of Clinical Nutrition.
Lead researcher Jessica Bayes, a PhD candidate in the UTS Faculty of Health, said the study was the first randomised clinical trial to assess the impact of a Mediterranean diet on the symptoms of depression in young men (aged 18-25).
“We were surprised by how willing the young men were to take on a new diet,” Bayes said. “Those assigned to the Mediterranean diet were able to significantly change their original diets, under the guidance of a nutritionist, over a short time frame.”
“It suggests that medical doctors and psychologists should consider referring depressed young men to a nutritionist or dietitian as an important component of treating clinical depression,” she said.
The study contributes to the emerging field of nutritional psychiatry, which aims to explore the effect that specific nutrients, foods and dietary patterns can have on mental health. The diet used in the study was rich in colourful vegetables, legumes and wholegrains, oily fish, olive oil and raw, unsalted nuts.
“The primary focus was on increasing diet quality with fresh wholefoods while reducing the intake of ‘fast’ foods, sugar and processed red meat,” Bayes said.
“There are lots of reasons why scientifically we think food affects mood. For example, around 90 per cent of serotonin, a chemical that helps us feel happy, is made in our gut by our gut microbes. There is emerging evidence that these microbes can communicate to the brain via the vagus nerve, in what is called the gut-brain axis.
“To have beneficial microbes, we need to feed them fibre, which is found in legumes, fruits and vegetables,” she said.
Roughly 30 per cent of depressed patients fail to adequately respond to standard treatments for major depressive disorder such as cognitive behaviour therapy and anti-depressant medications.
“Nearly all our participants stayed with the program, and many were keen to continue the diet once the study ended, which shows how effective, tolerable and worthwhile they found the intervention.”
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Materials provided by University of Technology Sydney. Note: Content may be edited for style and length.

Access to newer supermarkets that offer fresh foods in some of New York City’s poorest neighborhoods was linked to a 1% decline in obesity rates among public school students living nearby, a new study shows. The modernized markets were also tied to reductions of between 4% and 10% in the average student BMI-z score, a measure of body weight based on height for each age group by gender.
Although the differences were small, researchers say the results, if translated into policy changes, could have a meaningful difference if applied to the more than 14 million (19%) American children estimated to be obese, with rates highest among Black and Hispanic children.
To substantially lower death rates from related illnesses, researchers say childhood obesity rates would have to decline at least three times more than what was observed in the study. A broad health policy approach that also included subsidies for nutritious foods, restrictions on marketing of junk foods, and warning labels could potentially make up the difference.
Led by researchers at NYU Grossman School of Medicine, the new study showed that within a year after opening of newly renovated or new supermarkets, obesity rates dropped from 24.3% to 23.3% among 22,712 school-age children living within a half-mile of eight such stores. This reduction was compared with no change in obesity rates (steady at 23.3%) among 86,744 students who resided farther away from one of the publicly subsidized stores with more space for fresh produce and perishable foods. City grants have been available since 2009 to lower the cost of renovating or opening supermarkets in the city’s lowest-income neighborhoods.
“Our study highlights that one in four New York City public school kids sampled, predominantly Hispanic and Black, is obese, a worrisome sign of the depth of the problem facing children’s health in the city,” says study lead investigator and epidemiologist Pasquale Rummo, PhD, MPH. Childhood obesity is strongly linked to long-term risk of heart disease, stroke, and diabetes, says Rummo.
Among the study’s other key results was that obesity risk scores declined more among students in kindergarten through grade 8 than in students in grades 9 through 12.

Researchers at The University of Texas MD Anderson Cancer Center have identified a novel strategy to reduce immune-related adverse events from immunotherapy treatment by targeting the cytokine interleukin-6 (IL-6). The study, published today in Cancer Cell, establishes a proof of concept for combining immune checkpoint blockade with cytokine blockers to selectively inhibit inflammatory autoimmune responses.
While combination immunotherapy with anti-PD-1 and anti-CTLA-4 agents has revolutionized treatment for multiple cancer types, it also has high toxicity rates, which can affect quality of life and lead to treatment discontinuation. Often, patients whose cancers respond to combination immunotherapy also experience high-grade side effects. Immune-related enterocolitis (irEC), an inflammatory bowel condition, is the most common serious complication.
“We need to overcome immune toxicity, first and foremost, to support patients and reduce their symptom burden,” said senior author Adi Diab, M.D., associate professor of Melanoma Medical Oncology. “Secondly, we know that there are multiple, non-overlapping mechanisms of resistance in the tumor microenvironment. In order to build an effective multi-agent immunotherapy regimen, we have to overcome the barrier of immune-related toxicity so that patients can continue receiving the optimum treatment.”
The translational study analyzed patient tissue, preclinical models and retrospective data to determine how the IL-6 T-helper 17-cell (Th17) pathway contributes to toxicity and can be inhibited to separate the inflammatory autoimmune response from the antitumor immune response.
Preclinical studies reveal immunobiology of immune-related adverse events
IL-6 has been associated with immunotherapy resistance in preclinical models, but the mechanism was not well understood. IL-6 also is associated with several autoimmune diseases, and IL-6 blockers are approved to treat rheumatologic disorders and other autoimmune conditions.

Findings from a seven-year research project suggests that there could be a new approach to treating one of the most common and devasting forms of brain cancer in adults — Glioblastoma Multiforme (GBM).
In a peer-reviewed study published by BMC Cancer, scientists from the University of Surrey show that a short chain of amino acids (the HTL-001 peptide) is effective at targeting and inhibiting the function of a family of genes responsible for the growth of GBM — Hox genes. The study was conducted in cell and animal models.
The HTL-001 peptide used in the study has undergone safety testing and is suitable for patient trials. These trials are now being considered in GBM and other cancers.
Hardev Pandha, project lead and Professor of Medical Oncology at the University of Surrey, said:
“People who suffer from Glioblastoma Multiforme have a five per cent survival rate over a five-year period — a figure that has not improved in decades. While we are still early in the process, our seven-year project offers a glimmer of hope for finding a solution to Hox gene dysregulation, which is associated with the growth of GBM and other cancers, and which has proven to be elusive as a target for so many years.”
Ironically, Hox genes are responsible for the healthy growth of brain tissue but are ordinarily silenced at birth after vigorous activity in the growing embryo. However, if they are inappropriately ‘switched on’ again, their activity can lead to the progression of cancer. Hox gene dysregulation has long been recognised in GBM.
The project was carried out in collaboration with the universities of Surrey, Leeds and Texas, and HOX Therapeutics, a University of Surrey start-up company based on the University’s Surrey Research Park.
Professor Susan Short, co-author of the study from the University of Leeds, said:
“We desperately need new treatment avenues for these aggressive brain tumours. Targeting developmental genes like the HOX genes that are abnormally switched on in the tumour cells could be a novel and effective way to stop glioblastomas growing and becoming life-threatening.”
James Culverwell, CEO of HOX Therapeutics, said:
“HOX Therapeutics is excited to be associated with this project and we hope that with our continuing support, this research will eventually lead to novel and effective treatments for both brain and other cancers where HOX gene over-expression is a clear therapeutic target.”
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Materials provided by University of Surrey. Note: Content may be edited for style and length.

South Australian scientists have made a significant breakthrough in overcoming drug resistance in acute myeloid leukemia (AML), a rare and devastating blood cancer that kills most patients within a few years.
In a new study published in the world-leading hematology journal Blood, researchers from the University of South Australia and SA Pathology’s Centre for Cancer Biology describe how they have discovered a way to suppress a specific protein that promotes resistance to drugs commonly used to treat AML patients.
Professor Stuart Pitson, one of the lead authors of the study, says the finding could revolutionise the treatment of AML, a disease that has claimed the lives of Australian football great Russell Ebert, professional golfer Jarrod Lyle, high-profile American journalist Nora Ephron and filmmaker Lynn Shelton.
This year, it is estimated that 20,000 people in the United States and 900 people in Australia will be diagnosed with acute myeloid leukemia, a cancer of the blood and bone marrow characterised by an overproduction of cancerous white blood cells called leukaemic blasts.
Prof Pitson says these cells crowd out normal white blood cells, which then can’t do their usual infection-fighting work, thereby increasing the risk of infections, low oxygen levels and bleeding.
SA Pathology haematologist Associate Professor David Ross says many AML patients initially respond to Venetoclax, a new therapy for AML recently listed on the PBS, but over time AML cells become resistant to it.

In multicellular organisms, body cells adhere to each other to form tissues that perform various physiological functions. Epithelial cells form our skin and lining surfaces, such as the gut and other ducts, and protect our internal organs. To maintain the integrity of an organism and function properly, it is important for these cells to remain attached to each other. They do so through specific types of cellular junctions. These junctions are characterized by proteins, which also help in maintaining cellular identity. The loss of these proteins from cell surfaces causes them to lose their identity as epithelial cells, prompting their transformation into mesenchymal cells (through a process known as epithelial-mesenchymal transformation, or EMT), and subsequently, their progression towards cancer and fibrosis. These cancerous cells are only loosely adherent to each other (given that the proteins that helped maintain cellular adhesion are now lost), so they may separate from each other, migrate into the bloodstream, and cause the cancer to metastasize (spread to other parts of the body).
Now, while the role of proteins in maintaining cellular identity is well-researched, we can’t help but wonder-do lipids (fatty molecules) also play a role in characterizing cells and preventing EMT?
Under the guidance of Dr. Yoshikazu Nakamura and Dr. Kaori Kanemaru, researchers from Tokyo University of Science (TUS), Tokyo University of Pharmacy and Life Sciences, Tokyo Medical and Dental University, Akita University, Hokkaido University, and Kobe University have tried to find an answer to this question.
“We know lipids are an important class of biomolecules, necessary for certain cellular functions. One such lipid, a phosphatidylinositol, forms a phospholipid called phosphatidylinositol bisphosphate (PIP2),” Associate Professor Dr. Nakamura from TUS dives into the topic. He tells us that PIP2 is important because it is crucial for the formation of signaling molecules that regulate cell proliferation, survival, and migration. “We had evidence that higher amounts of PIP2 were found in the epidermal layer of skin, so we hypothesized that this phospholipid contributed to the properties and characterization of epithelial cells.”
The findings from their study have been published in Nature Communications. The paper describes how the team used a battery of analytical techniques including chromatography, mass spectroscopy, immunofluorescence, retroviral expression, and real-time quantitative PCR to confirm that PIP2 plays a critical role in the determination of epithelial identity.
“We saw that epithelial cells lost their properties when PIP2 was depleted from their cell membranes. On the other hand, osteosarcoma cells (which are cancerous, non-epithelial cells) gained epithelial cell-like properties when PIP2 was produced in their plasma membranes.” says Dr. Nakamura, with a look of excitement. The group was also able to show that PIP2 regulates these epithelial properties by recruiting Par3 — a protein which guides vesicles intracellularly — to the plasma membrane. Once in the plasma membrane, Par3 facilitates the formation of adherens junctions (one of the cellular junctions discussed above) which anchor neighboring cells together. This partially prevents EMT, and hence, progression of cancer.
“So,” Dr. Nakamura explains, “In theory, PIP2’s partial inhibition of EMT could halt cancer progression, making this phospholipid an attractive target molecule for anti-cancer treatment.”
TUS’ research has opened a new avenue for the development of anti-cancer drug development, possibly giving us a solution that will “stick.”
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Materials provided by Tokyo University of Science. Note: Content may be edited for style and length.

Young adults who were at risk of food insecurity had increased incidence of diabetes 10 years later, according to a Washington State University study.
While previous research has associated food insecurity with a range of health issues including diabetes, obesity and hypertension, this study showed a connection over time, suggesting a causal relationship.
In the study, published in the Journal of Nutrition, researchers analyzed data on nearly 4,000 people from the National Longitudinal Study of Adolescent to Adult Health. They found that adults ages 24-32 who said they’d been worried about food running out in the last year showed greater incidence of diabetes, either through blood glucose tests or self-reports, at ages 32-42, compared to those who did not report food insecurity risk.
“When we look at the data 10 years later, we do see this separation in prevalence of diabetes: those that experienced risk of food insecurity at young adulthood are more likely to have diabetes in middle adulthood,” said Cassandra Nguyen, the study’s lead author and an assistant professor with WSU’s Institute for Research and Education to Advance Community Health or IREACH.
While the study could not identify the exact reason for this connection, previous research has shown that food-insecure households often have diets with lower nutritional values.
“Eating according to the dietary guidelines tends to cost more money, and it may cost more time,” said Nguyen. “It’s not always accessible to households that have limitations such as transportation to sources of lower cost, nutritionally dense food.”
Nguyen added that people experiencing food insecurity can also get caught in a negative reinforcing cycle: when food insecurity is associated with a diet that contributes to disease risk, which then creates additional health care expenses, stressing a household’s economic resources and deepening food insecurity.