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Category Archives: Mind Building
Male infertility linked to prostate cancer risk
Men who have fertility treatment have a higher risk of prostate cancer in later life, a study suggests.
NHS will not pay for ‘life-changing’ migraine drug
Erenumab is the first drug specifically designed for preventing migraines.
Investigational drug with immunotherapy may provide new therapeutic opportunity for patients previously treated for kidney and lung cancer
Pegilodecakin, a first-in-class drug currently in clinical trials, has shown positive safety results and may offer a potential new treatment avenue for patients with non-small cell lung cancer (NSCLC) and kidney cancer. The study, led by The University of Texas MD Anderson Cancer Center, demonstrated that the drug, in combination with two leading anti-PD-1 monoclonal antibodies, pembrolizumab and nivolumab, achieved measurable responses for these patients.
Findings from a multi-center Phase Ib study was published in the Sept. 25 online issue of The Lancet Oncology.
“Pegilodecakin with anti-PD-1 monoclonal antibodies had a manageable toxicity profile and promising anti-tumor activity,” said Aung Naing, M.D., associate professor of Investigational Cancer Therapeutics. “Our study showed this combination demonstrated favorable response in NSCLC and kidney cancer patients who previously had been treated when compared to those treated with anti-PD-1 monoclonal antibodies alone.”
The study was designed to assess the safety, tolerability and maximal tolerated dose of pegilodecakin in combination with pembrolizumab or nivolumab, while also investigating biomarkers to identify patients likely to respond to treatment.
The study, which took place from February 2015 to September 2017, followed 111 kidney cancer, NSCLC and melanoma patients with advanced malignant solid tumors. The most common side effects were anemia, fatigue, low blood platelet counts and high triglycerides.
Objective responses were seen in 43% of NSCLC patients, 40% of kidney cancer patients and 10% of melanoma patients. Patients received pegilodecakin with pembrolizumab or nivolumab until disease progression, toxicity necessitating treatment discontinuation, patient withdrawal of consent or study end. Patients continued to receive combination therapy or pegilodecakin alone after disease progression if the investigator determined that the patient would continue to benefit.
Pegilodecakin is comprised of recombinant interleukin-10 (IL-10) which is linked to a molecule called polyethylene glycol (PEG). IL-10 is a protein that regulates activity of various immune cells, and high concentrations of IL-10 activate an immune response against cancer cells. The attachment of PEG to IL-10 increases its size, which prevents or delays its breakdown to prolong the time it circulates in the body.
The drug works by stimulating the survival, proliferation and “killing” potential of CD8+ T cells, known for their ability to recognize and destroy cancer cells. Increasing the amount of CD8+ T cells within the tumor is thought to improve prognosis and survival of the patient. The immune stimulatory effect of pegilodecakin complements the action of anti-PD-1 monoclonal antibodies that blocks the immune suppressive effect on T cells.
“The activity of pegilodecakin in combination with anti-PD-1 monoclonal antibodies introduces a new class of drugs to the treatment of advanced solid tumors,” said Naing. “Future randomized trials hopefully will determine the tolerability and clinical benefits of pegilodecakin as a single agent and in combinations in a range of cancers.”
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Materials provided by University of Texas M. D. Anderson Cancer Center. Note: Content may be edited for style and length.
AI helps scientists predict depression outcomes
The psychiatry field has long sought answers to explain why antidepressants help only some people.
Is a patient’s recovery due merely to a placebo effect — the self-fulfilling belief that a treatment will work — or can the biology of the person influence the outcome?
Two studies led by UT Southwestern provide evidence for the impact of biology by using artificial intelligence to identify patterns of brain activity that make people less responsive to certain antidepressants. Put simply, scientists showed they can use imaging of a patient’s brain to decide whether a medication is likely to be effective.
The studies include the latest findings from a large national trial (EMBARC) intended to establish biology-based, objective strategies to remedy mood disorders and minimize the trial and error of prescribing treatments. If successful, scientists envision using a battery of tests such as brain imaging and blood analyses to increase the odds of finding the right treatment.
“We need to end the guessing game and find objective measures for prescribing interventions that will work,” said Dr. Madhukar Trivedi, who oversees EMBARC and is founding Director of UT Southwestern’s Center for Depression Research and Clinical Care. “People with depression already suffer from hopelessness, and the problem can become worse if they take a medication that is ineffective.”
Brain activity
The studies — which each included more than 300 participants — used imaging to examine brain activity in both a resting state and during the processing of emotions. Both studies divided the participants into a healthy control group and people with depression who either received antidepressants or placebo.
Of the participants who received medication, researchers found correlations between how the brain is wired and whether a participant was likely to improve within two months of taking an antidepressant.
Dr. Trivedi said imaging the brain’s activity in various states was important to get a more accurate picture of how depression manifests in a particular patient. For some people, he said, the more relevant data will come from their brains’ resting state, while in others the emotional processing will be a critical component and a better predictor for whether an antidepressant will work.
“Depression is a complex disease that affects people in different ways,” he said. “Much like technology can identify us through fingerprints and facial scans, these studies show we can use imaging to identify specific signatures of depression in people.”
Improving outcomes
Data from both studies derive from the 16-week EMBARC trial, which Dr. Trivedi initiated in 2012 at four U.S. sites. The project evaluated patients with major depressive disorder through brain imaging and various DNA, blood, and other tests. His goal was to address a troubling finding from another study he led (STAR*D) that found up to two-thirds of patients do not adequately respond to their first antidepressant.
EMBARC’s first study, published in 2018, focused on how electrical activity in the brain can indicate whether a patient is likely to benefit from an SSRI (selective serotonin reuptake inhibitor), the most common class of antidepressant.
The finding has been followed by related research that identifies other predictive tests for SSRIs, most recently the resting-state brain imaging study published in the American Journal of Psychiatry and the second imaging study published in Nature Human Behaviour.
AI and depression
The Nature research used artificial intelligence to determine correlations between the effectiveness of an antidepressant and how a patient’s brain processes emotional conflict.
Participants undergoing brain imaging were shown photographs in quick succession that offered sometimes conflicting messages such as an angry face with the word “happy,” or vice versa. Each participant was asked to read the word on the photograph before clicking to the next image.
However, rather than observe only neural regions believed to be relevant to predicting antidepressant benefits, scientists used machine learning to analyze activity in the entire brain. “Our hypotheses for where to look have not panned out, so we wanted to try something different,” Dr. Trivedi explained.
AI identified specific brain regions — for example in the lateral prefrontal cortices — that were most important in predicting whether participants would benefit from an SSRI. The results showed that participants who had abnormal neural responses during emotional conflict were less likely to improve within eight weeks of starting the medication.
Ongoing research
Dr. Trivedi has initiated other large research projects to further understand the underpinnings of mood disorders, among them D2K, a study that will enroll 2,500 patients with depression and bipolar disorders and follow them for 20 years. In addition, RAD is a 10-year study of 2,500 participants (ages 10-24) that will uncover factors for reducing the risk of developing mood or anxiety disorders.
Utilizing some of these enrollees, Dr. Trivedi’s research team will study the results from several other tests to augment brain imaging and more accurately assess patients’ biological signatures to determine the most effective treatment. Dr. Trivedi has had preliminary success developing a blood test but acknowledges it may only benefit patients with a specific type of inflammation.
Combining blood and brain tests, he said, will improve the chances of choosing the right treatment the first time.
“We need to look at this issue in several ways to identify the many different signatures of depression in the body,” he said. “The findings from these new studies are significant and bring us closer to using them clinically to improve outcomes for millions of people.”
A black hole’s warped world
A new new visualization of a black hole illustrates how its gravity distorts our view, warping its surroundings as if seen in a carnival mirror. The visualization simulates the appearance of a black hole where infalling matter has collected into a thin, hot structure called an accretion disk. The black hole’s extreme gravity skews light emitted by different regions of the disk, producing the misshapen appearance.
Bright knots constantly form and dissipate in the disk as magnetic fields wind and twist through the churning gas. Nearest the black hole, the gas orbits at close to the speed of light, while the outer portions spin a bit more slowly. This difference stretches and shears the bright knots, producing light and dark lanes in the disk.
Viewed from the side, the disk looks brighter on the left than it does on the right. Glowing gas on the left side of the disk moves toward us so fast that the effects of Einstein’s relativity give it a boost in brightness; the opposite happens on the right side, where gas moving away us becomes slightly dimmer. This asymmetry disappears when we see the disk exactly face on because, from that perspective, none of the material is moving along our line of sight.
Closest to the black hole, the gravitational light-bending becomes so excessive that we can see the underside of the disk as a bright ring of light seemingly outlining the black hole. This so-called “photon ring” is composed of multiple rings, which grow progressively fainter and thinner, from light that has circled the black hole two, three, or even more times before escaping to reach our eyes. Because the black hole modeled in this visualization is spherical, the photon ring looks nearly circular and identical from any viewing angle. Inside the photon ring is the black hole’s shadow, an area roughly twice the size of the event horizon — its point of no return.
“Simulations and movies like these really help us visualize what Einstein meant when he said that gravity warps the fabric of space and time,” explains Jeremy Schnittman, who generated these gorgeous images using custom software at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. “Until very recently, these visualizations were limited to our imagination and computer programs. I never thought that it would be possible to see a real black hole.” Yet on April 10, the Event Horizon Telescope team released the first-ever image of a black hole’s shadow using radio observations of the heart of the galaxy M87.
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Materials provided by NASA/Goddard Space Flight Center. Original written by Francis Reddy. Note: Content may be edited for style and length.
Health24.com | How do high-fat diets increase your appetite?
Most people are aware of the risks associated with high-fat diets such as problems with your heart health, obesity and compromising your immune system.
High-fat diets have also been linked to unfavourable changes in the type and number of gut bacteria – and now researchers are saying it can contribute to irregularities in the hypothalamus region of the brain, which is responsible for controlling body temperature, hunger, thirst, emotions, sleep, appetite and digestion.
Malnutrition and obesity
The study, published in Cell Metabolism was conducted by researchers from Yale University and it looked at how a diet high in fat – specifically diets high in fats and carbohydrates – stimulates hypothalamic inflammation, which is a physical response to malnutrition and obesity.
This results in changes in the metabolism and causes you to eat more. The study was led by Sabrina Diano, the Richard Sackler Family Professor of Cellular & Molecular Physiology and professor of neuroscience and comparative medicine.
Researchers found that inflammation occurs in the hypothalamus after three days of consumption of a high-fat diet. Diano, a member of the Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism said: “We were intrigued by the fact that these are very fast changes that occur even before the body weight changes, and we wanted to understand the underlying cellular mechanism.”
Looking at inflammation of the hypothalamus in animals on a high-fat diet, the researchers found that changes were taking place in the physical structure of their microglial cells. Microglial cells act as the first line of defence in the central nervous system, regulating inflammation.
In order to see how diet affects the brain, researchers gave some rodents diets high in fats and carbohydrates, while others were given “regular” mouse food.
Inflammatory signal
Researchers found that the effect of the microglia springing into action was that neurons received an inflammatory signal, which lead to the mice eating more food. Eventually, the mice became obese.
The study indicated that high-fat diets do not only affect people physically but it also emphasises that an unhealthy diet can alter food intake neurologically. “There are specific brain mechanisms that get activated when we expose ourselves to specific types of foods. This is a mechanism that may be important from an evolutionary point of view. However, when food rich in fat and carbs is constantly available it is detrimental.”
Researchers would like to conduct more studies about the connection between the microglia and diseases of the brain, such as Alzheimer’s disease. This neurological condition has been linked to changes in microglial cells, according to the National Institute of Health.
Image credit: iStock
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Health24.com | Clues to why women have higher odds for Alzheimer’s
Rates of Alzheimer’s disease are higher in women than in men, and researchers now think they know why.
A team from Vanderbilt University Medical Center, in Nashville, Tennessee, has identified gender differences in how the Alzheimer’s-related protein tau spreads in the brain.
A graph analysis
Research suggests that tau spreads through the brain like an infection, moving from neuron to neuron and turning other proteins into abnormal tangles that result in the death of brain cells.
In this study, investigators used data from positron emission tomography (PET) scans of healthy people and patients with mild mental (cognitive) impairment to create a graph analysis of how tau spreads.
“It’s kind of like reconstructing a crime scene after a crime. You weren’t there when it happened, but you can determine where an intruder entered a house and what room they entered next,” said lead investigator Sepi Shokouhi, an assistant professor of psychiatry and behavioural sciences.
“The graph analysis does something similar to show how tau spreads from one region to another,” Shokouhi explained in a centre news release.
The researchers found that the structure of tau networks is different in men and women, with women having a larger number of “bridging regions” that connect various areas of the brain.
Further research needed
This may enable tau to spread more easily between brain regions, increasing the speed at which it accumulates and putting women at greater risk for Alzheimer’s disease, the investigators theorised.
The study was presented at the Alzheimer’s Association International Conference, in Los Angeles. Data presented at conferences is usually considered preliminary until published in a peer-reviewed medical journal.
Further research is needed to confirm that women have an accelerated spread of tau. If it’s proven, then sex-specific approaches may be needed to prevent Alzheimer’s, according to the researchers. This could include earlier treatment, lifestyle interventions and/or remedial help for memory.
“Understanding how different biological processes influence our memory is a really important topic,” Shokouhi said.
Image credit: iStock
Health24.com | How to relieve dry, irritated eyes
Do all the ads for dry eye relief have you thinking you could have this condition? If you’ve ever felt like you had a grain of sand in your eye when nowhere close to the beach, you could be experiencing dry eye.
Exactly what is dry eye? Simply put, it’s when you aren’t making enough tears to keep the front surface of the eye lubricated, or your tears don’t have enough water in them. Eyes can feel gritty, scratchy or like they’re burning. You might even notice excess watering or blurred vision.
There’s a lot you can do
Tear production often lessens with age, but it can also be the result of a medical condition – not only eye diseases but also rheumatoid arthritis, diabetes and thyroid problems. It can also be a side effect of certain medications, including antihistamines, decongestants, blood pressure medications and antidepressants. Living in a dry, windy climate or just sitting in front of a cosy fireplace in winter can cause tears to evaporate.
There’s much you can do to restore the normal amount of tears, according to the American Optometric Association, starting with over-the-counter artificial tear solutions, or prescription eye drops or ointments. See your eye professional to discuss the options and find out what’s most appropriate for you.
Lifestyle changes can also help. Try getting more omega-3 fatty acids in your diet. Treat your eyes to warm compresses and massage your eyelids. If you wear contact lenses, new formulations might be more comfortable. Blink regularly when reading or working at a computer for long periods of time. Also, increase the humidity in the air at work and at home, wear sunglasses to shield eyes outdoors, and drink eight to 10 glasses of water each day to stay hydrated.
Image credit: iStock
Repeat Caesareans ‘often safer birth option’
Mothers should be offered a choice of vaginal or Caesarean delivery and be told about the risks, say experts.
