Athenahealth, which has said it initiated a process to explore strategic alternatives, is asking for initial bids this week, said Dealreporter, according to contacts.
Wednesday, July 11, 2018
Galmed started at buy by Cantor
Galmed initiated with an Overweight at Cantor Fitzgerald. Cantor analyst Elemer Piros initiated Galmed with an Overweight and $59 price target.
‘Big Bang’ of Alzheimer’s: Genesis of disease, shape-shifting tau IDd
Scientists have discovered a “Big Bang” of Alzheimer’s disease – the precise point at which a healthy protein becomes toxic but has not yet formed deadly tangles in the brain.
A study from UT Southwestern’s O’Donnell Brain Institute provides novel insight into the shape-shifting nature of a tau molecule just before it begins sticking to itself to form larger aggregates. The revelation offers a new strategy to detect the devastating disease before it takes hold and has spawned an effort to develop treatments that stabilize tau proteins before they shift shape.
“This is perhaps the biggest finding we have made to date, though it will likely be some time before any benefits materialize in the clinic. This changes much of how we think about the problem,” said Dr. Marc Diamond, Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases and a leading dementia expert credited with determining that tau acts like a prion – an infectious protein that can self-replicate.
The study published in eLife contradicts the previous belief that an isolated tau protein has no distinct shape and is only harmful after it begins to assemble with other tau proteins to form the distinct tangles seen in the brains of Alzheimer’s patients.
Scientists made the discovery after extracting tau proteins from human brains and isolating them as single molecules. They found that the harmful form of tau exposes a part of itself that is normally folded inside. This exposed portion causes it to stick to other tau proteins, enabling the formation of tangles that kill neurons.
“We think of this as the Big Bang of tau pathology,” said Dr. Diamond, referring to the prevailing scientific theory about the formation of the universe. “This is a way of peering to the very beginning of the disease process. It moves us backward to a very discreet point where we see the appearance of the first molecular change that leads to neurodegeneration in Alzheimer’s. This work relied on a close collaboration with my colleague, Dr. Lukasz Joachimiak.”
Despite billions of dollars spent on clinical trials through the decades, Alzheimer’s disease remains one of the most devastating and baffling diseases in the world, affecting more than 5 million Americans alone.
Dr. Diamond is hopeful the scientific field has turned a corner, noting that identifying the genesis of the disease provides scientists a vital target in diagnosing the condition at its earliest stage, before the symptoms of memory loss and cognitive decline become apparent.
His team’s next steps are to develop a simple clinical test that examines a patient’s blood or spinal fluid to detect the first biological signs of the abnormal tau protein. But just as important, Dr. Diamond said, efforts are underway to develop a treatment that would make the diagnosis actionable.
He cites a compelling reason for cautious optimism: Tafamidis, a recently approved drug, stabilizes a different shape-shifting protein called transthyretin that causes deadly protein accumulation in the heart, similar to how tau overwhelms the brain.
“The hunt is on to build on this finding and make a treatment that blocks the neurodegeneration process where it begins,” Dr. Diamond said. “If it works, the incidence of Alzheimer’s disease could be substantially reduced. That would be amazing.”
Dr. Diamond’s lab, at the forefront of many notable findings relating to tau, previously determined that tau acts like a prion – an infectious protein that can spread like a virus through the brain. The lab has determined that tau protein in the human brain can form many distinct strains, or self-replicating structures, and developed methods to reproduce them in the laboratory. He said his newest research indicates that a single pathological form of tau protein may have multiple possible shapes, each associated with a different form of dementia.
More information: Hilda Mirbaha et al. Inert and seed-competent tau monomers suggest structural origins of aggregation, eLife (2018). DOI: 10.7554/eLife.36584
Footwear habits influence child and adolescent motor skill development
New research finds that children and adolescents who spend most of their time barefoot develop motor skills differently from those who habitually wear shoes. Published in Frontiers in Pediatrics, this is the first study to assess the relevance of growing up shod vs. barefoot on jumping, balancing and sprinting motor performance during different stages of childhood and adolescence. The study shows that habitually barefoot children are noticeably better at jumping and balancing compared to habitually shod children, particularly from 6-10 years of age. While these beneficial barefoot effects diminished in older adolescents, the research nevertheless highlights the importance of barefoot exercise for motor development as children grow and mature.
“Walking barefoot is widely thought to be more natural, and the use of footwear has long been discussed as an influencing factor on foot health and movement pattern development,” explains Professor Astrid Zech from the University of Jena, Germany, who led the study.
“A few studies report that barefoot situations change biomechanics in children and adults during running and jumping—but only limited knowledge exists for the clinical relevance of this finding,” she continues. “We wanted to investigate, for the first time, whether changes in foot biomechanics due to barefoot activities are actually relevant for the development of basic motor skills during childhood and adolescence.”
Zech, together with two research teams, assessed three motor skills—balance, standing long jump and a-20 m sprint—in 810 children and adolescents from 22 primary and secondary schools across rural Western Cape South Africa and urban areas of northern Germany. The two groups were selected to represent different footwear lifestyles: children from South Africa are habitually barefoot, while children from Germany wear shoes most of the time.
The habitually barefoot participants scored significantly higher in the balance and jumping tests compared to the habitually shod participants. This difference was observed in both test conditions (barefoot and shod) and across all age groups (6-10, 11-14 and 15-18 years), but particularly evident in 6-10 year-old children. The habitually barefoot children also performed better when barefoot than when shod.
“Most of the primary school children in our study (South Africa) go to school and perform sport and leisure activities barefoot,” says Professor Ranel Venter from Stellenbosch University, who led the South African research team. “Our finding that these children performed better in balancing and jumping supports the hypothesis that the development of basic motor skills during childhood and adolescence at least partly depends on regular barefoot activities.”
The results for the sprint test, however, were different. Here the habitually shod children performed better, particularly those in the 11-14 year age group, and both groups performed better while shod. The researchers explain that environment—the one factor that could not be standardized across the two study locations—may have influenced this result.
“In South Africa, the sprint test took place outdoors—with different weather conditions and surfaces. In contrast, the German children took the sprint test indoors, mostly in a sports hall with a sprung floor,” says Zech. “The type of shoe may also have influenced the results. South African students run in school shoes, while German students use sneakers or athletic shoes in their physical education classes. So while our results suggest that growing up shod may be beneficial for fast sprinting, we need to investigate this further.”
Overall, the researchers’ work emphasises the benefits of barefoot physical activities for motor development.
“Physical education classes, exercise and sport programs, and reactional activities that aim to improve basic motor skills could benefit from including barefoot activities,” says Zech. “Parents could also encourage regular barefoot time at home.”
More information: Astrid Zech et al, Motor Skills of Children and Adolescents Are Influenced by Growing up Barefoot or Shod, Frontiers in Pediatrics (2018). DOI: 10.3389/fped.2018.00115
Engineered cancer cells can fight primary and metastatic cancer
What if cancer cells could be re-engineered to turn against their own kind? A new study led by researchers at Brigham and Women’s Hospital leverages the power of gene editing to take a critical step toward using cancer cells to kill cancer. The team reports promising results in preclinical models across multiple types of cancer cells, establishing a potential roadmap toward clinical translation for treating primary, recurrent and metastatic cancer. Results are published in Science Translational Medicine.
“This is just the tip of the iceberg,” said corresponding author Khalid Shah MS, Ph.D., director of the Center for Stem Cell Therapeutics and Imaging (CSTI) in the BWH Department of Neurosurgery and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI). “Cell-based therapies hold tremendous promise for delivering therapeutic agents to tumors and may provide treatment options where standard therapy has failed. With our technique, we show it is possible to reverse-engineer a patient’s own cancer cells and use them to treat cancer. We think this has many implications and could be applicable across all cancer cell types.”
The new approach capitalizes on cancer cells‘ self-homing ability—the process in which cancer cells can track the cells of their kind that have spread within the same organ or to other parts of the body. Harnessing this power could overcome drug delivery challenges, helping get therapeutics to tumor sites that may otherwise be difficult to reach.
The team developed and tested two techniques to harness the power of cancer cells. The “off the shelf” technique used pre-engineered tumor cells that would need to be matched to a patient’s HLA phenotype (essentially, a person’s immune fingerprint). The “autologous” approach used CRISPR technology to edit the genome of a patient’s cancer cells and insert therapeutic molecules. These cells could then be transferred back into the patient.
To test both approaches, the team used mouse models of primary and recurrent brain cancer and breast cancer that has spread to the brain. The team saw direct migration of engineered cells to the sites of tumors and found evidence that the engineered cells specifically targeted and killed recurrent and metastatic cancer in the mice. The researchers report that the treatment increased the survival of the mice. Engineered cells were equipped with a “kill switch” that could be activated after treatment—PET imaging showed that this kill switch worked to eliminate the cells.
“Our study demonstrates the therapeutic potential of using engineered tumor cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers,” said Shah.
Explore further: How targeting metabolism can defeat cancer stem cells
More information: C. Reinshagen el al., “CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors,” Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aao3240
Hep C vaccine could dramatically reduce transmission in people who inject drugs
Among the most serious consequences of the opioid epidemic is the spread of hepatitis C among injecting drug users.
A major new study shows that if a hepatitis C vaccine were successfully developed, it would dramatically reduce transmission of hepatitis C among drug users—even though it’s unlikely such a vaccine would provide complete immunity.
The study, which employed mathematical modeling, is published in Science Translational Medicine.
Four of the study’s authors are members of the Program for Experimental and Theoretical Modeling in the division of hepatology of Loyola Medicine and Loyola University Chicago Stritch School of Medicine. One of the Loyola researchers, Harel Dahari, Ph.D., is a co-senior author of the study, along with Marian Major, Ph.D., of the U.S. Food and Drug Administration. Dr. Dahari is an assistant professor at Loyola University Chicago Stritch School of Medicine.
Vaccines are currently available for hepatitis A and hepatitis B, but a vaccine for hepatitis C is still under investigation. A clinical trial is testing an experimental hepatitis C vaccine on injecting drug users. Unlike many other vaccines, the hepatitis C vaccine is not expected to provide complete immunity, known as sterilizing immunity. A vaccinated person exposed to HCV could still be infected with the virus, although the amount of virus in the bloodstream would be significantly reduced.
The new study calculated how effective a vaccine that provided incomplete immunity would be in preventing transmission among injecting drug users. Researchers developed a mathematical model to determine transmission probabilities in drug users who share needles and syringes. They simulated the sharing of two types of common syringes used by drug users. Using previously published data from people infected or reinfected with hepatitis C virus, researchers then estimated the transmission risks between injecting drug users.
The study estimated that if an injecting drug user shared a syringe/needle with a second drug user who was infected with hepatitis C, there would be a greater than 90 percent chance the first drug user would also become infected with hepatitis C after six months. However, if a vaccine were used, the transmission risk would decrease to between 1 and 25 percent, depending on the type of needle used and other factors.
“Our findings suggest that a hepatitis C vaccine would be an essential part of a comprehensive prevention strategy to meet the World Health Organization’s goal of eradicating hepatitis C by 2030,” said study co-author Scott Cotler, MD, head of Loyola’s division of hepatology and a professor in the department of medicine of Loyola University Chicago Stritch School of Medicine. Other Loyola co-authors are mathematical modelers Alexander (Sasha) Gutfraind, Ph.D., and Louis Shekhtman, MSc.
Hepatitis C is caused by the hepatitis C virus (HCV). Long-term infection with HCV, known as chronic hepatitis C, usually is silent for many years. But the disease eventually can cause cirrhosis (advanced scarring) of the liver, liver cancer and liver failure. In the United States, as many as 3 million people are chronically infected with HCV, with more than 30,000 new infections per year.
Hepatitis C spreads through contaminated blood, and an estimated 60 percent of HCV infections in the U.S. are attributed to sharing needles, syringes or other drug paraphernalia.
Antiviral drugs are used to treat hepatitis C, with cure rates higher than 90 percent. In addition to stopping the disease from progressing, antivirals also can prevent transmission. However, antivirals are expensive, and many injecting drug users lack access to healthcare in the U.S. And even if they are cured, injecting drug users can become infected again if they continue to share needles.
“While extremely effective, antivirals alone are unlikely to eliminate hepatitis C globally,” Dr. Dahari said. “We need to combine antivirals with a hepatitis C vaccine and harm-reduction measures such as needle-syringe exchange programs, opioid substitution therapy and behavioral counseling.”
Some people think a vaccine needs to be perfect, Dr. Dahari added. “But we found that a vaccine still can be extremely beneficial even if it does not provide complete sterilizing immunity.”
More information: M. Major el al., “Modeling of patient virus titers suggests that availability of a vaccine could reduce hepatitis C virus transmission among injecting drug users,” Science Translational Medicine (2018). stm.sciencemag.org/lookup/doi/ … scitranslmed.aao4496
Soccer headers may be linked to balance problems
Soccer players who head the ball more often may be more likely to have balance problems than players who do not head the ball as often, according to a preliminary study released today that will be presented at the American Academy of Neurology’s Sports Concussion Conference in Indianapolis July 20 to 22, 2018.
“Soccer headers are repetitive subconcussive head impacts that may be associated with problems with thinking and memory skills and structural changes in the white matter of the brain,” said study author John Jeka, Ph.D., of the University of Delaware in Newark, Del. “But the effect of headers on balance control has not been studied.”
For the study, 20 soccer players recruited from the community in Newark took a balance test where they walked along a foam walkway with their eyes closed under two conditions: with galvanic vestibular stimulation (GVS) and without GVS. For GVS, electrodes placed behind each ear stimulate the nerves that send messages from the balance system in the inner ear to the brain. So the stimulator can make you feel like you are moving when you are not. In this case, it made participants feel like they were falling sideways.
The soccer players, who had an average age of 22, also completed questionnaires about how many times they had headed the ball during the past year. The number of headers over a year for each participant ranged from 16 to 2,100, with an average of 451 headers. Those numbers were calculated by asking participants for the average number of headers during a practice and game, the average number of practices and games per week, and the average number of months per year that the player participated.
The study found that the players with the largest number of headers had the largest balance responses to GVS in both foot placement and hip adduction during the walking test, which indicated that they had vestibular processing and balance recovery problems. Researchers found for every 500 headers, foot placement response increased about 9 millimeters and hip adduction response increased about 0.2 degrees.
“Soccer players must have good balance to play the game well, yet our research suggests that headers may be undermining balance, which is key to all movement, and yet another problem now linked to headers,” said study author Fernando V. Santos, PT, of the University of Delaware. “It is important that additional research be done to look more closely at this possible link with balance and to confirm our findings in larger groups of people.”
A limitation of the study was that participants relied on memory when reporting how many times they headed the ball.
Explore further: Heading—not collisions—cognitively impairs players
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