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Monthly Archives: November 2016

Cognitive Training Benefits in Dementia

“The effects of cognitive training in dementia patients have been studied actively during recent decades but the quality and reliability of the studies varies,” says licenced neuropsychologist Eeva-Liisa Kallio. She reviewed 31 randomized controlled trials on cognitive training in dementia patients.

Kallio’s reserch paper “Cognitive Training Interventions for Patients with Alzheimer’s Disease: A Systematic Review” was published inJournal of Alzheimer’s Disease.

Some of the studies in the review focused primarily on cognitive training and in others cognitive training was part of broader cognitive or multi-component intervention.

“Many of the studies reported effects on cognitive functions immediately after the intervention but only few studies included follow-up of the patients or showed improvement in cognitive functions that were not directly linked to the skills trained in the intervention,” Kallio says.

In the studies, cognitive functioning was measured before and after the intervention. Also questionnaires on psychological wellbeing, quality of life and activities of daily living were used.

According to Kallio’s review, the data from the previous studies is not adequate to give any recommendations on the use of cognitive training in the treatment of dementia patients. Even though the scientific evidence remains scarce, the studies do suggest that the training should be intensive or focus primarily on a particular aspect of cognitive functions.

“Healthy adults can get limited benefits from cognitive training but we need more high quality trials to confirm cognitive training as an effective treatment option in dementia,” Kallio says.

She belongs to the University of Helsinki’s FINCOG research group, led by professor Kaisu Pitkälä. The next step in the project is to study the effects of intensive, 3-month cognitive training on the community-dwelling older persons with dementia participating in adult day care activities organised by the City of Helsinki.

In this randomized controlled trial, part of the participants attend systematic cognitive training while their control group participates in the normal day care activities.

In addition to cognitive functions, also indicators of quality of life and activities of daily living are used and the measurements are repeated six months after the intervention. The research also includes a 24-month health register follow-up.

“Cognitive training is quite easy to implement. If our research suggests that the participants benefit from it, cognitive training can be easily included in the adult day care activities,” Kallio says.

Read Emotions From The Eye Sees

“Our findings show that how we see directly relates to how others see us, through our facial expressions,” says psychological scientist Daniel H. Lee of the University of Colorado Boulder. “This is a clear demonstration of emotional embodiment, from sender to receiver.”

“For example, if you’re watching ‘Curb Your Enthusiasm’ and wonder why when Larry David squints his eyes that conveys scrutiny, our work offers a theory that explains it,” Lee explains. “Narrowing the eyes for visual scrutiny also communicates scrutiny.”

The idea that our facial expressions communicate emotion isn’t new — but Lee and co-author Adam K. Anderson of Cornell University wanted to understand how our expressions came to communicate so many complex emotions and mental states.

“We went back to Darwin,” says Lee. “His theories on how expression appearance evolved to have a sensory function for the sender showed how it also co-evolved to have communication function for the receiver.”

Opening our eyes wide boosts visual sensitivity by allowing more light in, helping us to see any threats that might lurk nearby. Narrowing our eyes to a squint, on the other hand, can increase visual acuity, helping us to discriminate fine details. Lee and Anderson hypothesized that these opposing types of expressions, which originated for optical purposes, may have been co-opted for social purposes, operating as signals of conceptually related mental states.

Using photos of faces included in widely-used databases, the researchers created average exemplars of six expressions (i.e., sadness, disgust, anger, joy, fear, surprise). On each trial, participants saw a pair of eyes (one of the six exemplars) and a word representing a specific mental state, and they rated the extent to which the mental-state term described the eye expression. Each participant completed a total of 600 trials. The researchers then analyzed how these mental state perceptions related to specific eye features: the openness of the eye; the distance from the eyebrow to the eye; the slope and curve of the eyebrow; and wrinkles around the nose, the temple, and below the eye.

Combined ratings from the 28 participants showed that the eyes really do provide a strong signal of emotional state. People consistently matched the eye expressions with the corresponding basic emotion, rating “fear” as a strong match for the fear eye expression, for example. And these ratings were reliably higher than those for other mental states paired with the same eye expression.

Additional analyses examining the relationship between specific eye features and mental states revealed four distinct clusters, two of which aligned with eye-narrowing and eye-widening features. The eye-narrowing cluster was associated with mental states related to social discrimination, including hate, suspicion, aggressiveness, and contempt. The eye-widening cluster was associated with mental states related to information sensitivity, including awe, anticipation, cowardice, and interest.

The fact that these two clusters associated so strongly around eye widening and narrowing surprised the researchers:

“Human expressions are highly complex — when enumerating our facial muscles, we computed that there are at least 3.7 x 1016different expression combinations, which is about the same probabilistic space as two Powerball jackpots,” says Lee. “We looked at a subset of this space — just the eye region — and found that one simple physical dimension (widening vs. narrowing) explained a majority of this complex space in social communication.”

Two additional clusters included eye features associated with joy, which aligned with positive mental states like admiration, and sadness, which aligned with negative mental states like uneasiness.

Findings from a second study showed that the eyes provide equally strong emotional signals when they’re embedded in the context of a whole face, even when the features in the lower face don’t indicate the same expression as the eyes do.

Thus, relative to the rest of our facial features, the eyes seem to have it when it comes to conveying complex mental states.

“This finding underscores how the origins of reading mental states from the eyes relate in part to how the eyes see,” the researchers write.

Proteins in nose could reveal a infection

Duke Health scientists have identified a group of proteins that, when detected in specific quantities in the mucous, are 86 percent accurate in confirming the infection is from a cold or flu virus, according to a small, proof-of-concept trial published online in the journal EBioMedicine.

The researchers hope their initial work identifying the protein signature could aid the development of a quick, noninvasive doctor’s office test to determine the cause of upper respiratory illness and appropriate treatment.

“Every day, people are taking time off from work, going to emergency rooms, urgent care or their primary care doctors with symptoms of an upper respiratory infection,” said Geoffrey S. Ginsburg, M.D., Ph.D., a senior author of the paper and director of the Duke Center for Applied Genomics & Precision Medicine (DCAGPM), which led the study. “Looking for these proteins could be a relatively easy and inexpensive way of learning if a person has a viral infection, and if not, whether the use of antibiotics is appropriate.”

Although upper respiratory infections are among the most common reasons people visit the doctor in the U.S., health care providers lack tools to distinguish between a bacterial infection that might warrant antibiotics and a viral infection that would instead call for symptom relief.

Widespread use of antibiotics for upper respiratory infections don’t benefit patients with viral illness and can contribute to antibiotic-resistant superbugs, Ginsburg said. More precise diagnoses of these infections could be another tool to curb the development of superbugs, he said.

For the trial, researchers infected 88 healthy adult volunteers with a common strain of cold or flu virus.

Some participants didn’t get sick. Among those who developed infections, researchers found a distinct set of 25 proteins in fluid samples they gathered by flushing about 2 teaspoons of saline through the participant’s nasal passages.

Duke researchers in genomics and precision medicine have spent the past decade exploring strategies for differentiating bacterial and viral infections with the goal of developing cost-effective diagnostic tools doctors could use in their offices.

“In the past, science has focused on identifying the pathogen someone is infected with in the blood or other sample,” said lead author Thomas Burke, Ph.D., director of technology advancement and diagnostics at the DCAGPM. “Our approach flips the paradigm of how we look for infection. Instead of looking for the pathogen, we study the individual’s response to that pathogen and signature patterns in their genes, proteins, metabolites and other biomarkers.”

The Duke team has previously explored blood tests to examine a patient’s RNA for gene signatures to distinguish bacterial and viral infections in the upper respiratory tract and is working with a private company to develop potential diagnostics.

Analyzing proteins in mucous is a less invasive approach and requires less processing than blood samples. The researchers hope additional studies verify the initial results and lead to the development of a paper-based test that could be used in doctor’s offices or even at home to determine whether a doctor’s visit is necessary, said Christopher Woods, M.D., a senior author and associate director of applied genomics at the DCAGPM.

“The protein targets offer a faster, more cost-effective model for rapid screening and diagnoses of viral infections,” Woods said. “If the data are verified, the model could be valuable in many circumstances, such as rural settings or developing countries with less convenient access to health care, or even as an airport screening tool during an outbreak of a particularly threatening strain of flu.”

Protein once thought exclusive to neurons helps some cancers grow

UT Southwestern Medical Center researchers report those findings in two recent studies, one in the Proceedings of the National Academy of Sciences (PNAS) and the second in Developmental Cell

“Many properties of aggressive cancer growth are driven by altered cell signaling,” said Dr. Sandra Schmid, senior author of both papers and Chair of Cell Biology at UT Southwestern. “We found that cancer cells are taking a page from the neuron’s signaling playbook to maintain certain beneficial signals and to squelch signals that would harm the cancer cells.”

The two studies find that dynamin1 (Dyn1) — a protein once thought to be present only in nerve cells of the brain and spinal cord — is also found in aggressive cancer cells. In nerve cells, or neurons, Dyn1 helps sustain neural transmission by causing rapid endocytosis — the uptake of signaling molecules and receptors into the cell — and their recycling back to the cell surface. These processes ensure that the neurons keep healthy supplies at the ready to refire in rapid succession and also help to amplify or suppress important nerve signals as necessary, Dr. Schmid explained.

“This role is what the cancer cells have figured out. Aggressive cancer cells have usurped the mechanisms that neurons use for the rapid uptake and recycling of neural transmitters. Instead of neural transmitters, the cancer cells use Dyn1 for rapid uptake and recycling of EGF (epidermal growth factor) receptors. Mutations in EGF receptors are drivers of breast and lung cancers,” she said of the Developmental Cell study.

In order to thrive, cancer cells must multiply faster than nearby noncancerous cells. EGF receptors help them do that, she explained.

Cancer cell survival is another factor in disease progression. In thePNAS study, the Schmid lab found that aggressive cancer cells appear to have adapted neuronal mechanisms to thwart a key cancer-killing pathway triggered by activating “death receptors” (DRs) on cancer cells. Specifically, aggressive cancer cells appear to have adapted ways to selectively activate Dyn1 to suppress DR signaling that usually leads to cancer cell death.

“It is amazing that the aggressive cancers use a signaling pathway to increase the activity of EGF and also turn on Dyn1 pathways to suppress cancer death — so you have this vicious circle,” said Dr. Schmid, who holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology.

She stressed that less aggressive cancers respond to forms of chemotherapy that repress EGF signaling and/or die in response to the TRAIL-DR pathway. However, aggressive lung and breast cancer cells have adapted ways to commandeer the neuronal mechanisms identified in these studies.

The hope is that this research will someday lead to improved strategies to fight the most aggressive cancers, she said. Currently, her laboratory is conducting research to identify Dyn1 inhibitors as potential anticancer drugs using a 280,000-compound library in a shared facility at UT Southwestern.

“Cancer is a disease of cell biology. To grow, spread, and survive, cancer cells modify normal cellular behavior to their advantage. They can’t reinvent the underlying mechanisms, but can adapt them. In these studies, we find that some cancer cells repurpose tools that neurons use in order to get a competitive advantage over nearby normal cells,” she said.