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Surprising number of businesses selling unapproved stem cell ‘treatments’ in the US

At least 351 companies across the United States are marketing unapproved stem cell procedures at 570 individual clinics. Such businesses advertise “stem cell” interventions for orthopedic injuries, neurological disorders, cardiac diseases, immunological conditions, pulmonary disorders, injured spinal cords, and cosmetic indications. In Cell Stem Cell on June 30, bioethicist Leigh Turner (@LeighGTurner) and stem cell researcher Paul Knoepfler (@pknoepfler) present an analysis of U.S. businesses engaged in “direct-to-consumer” marketing of these procedures.

“In almost every state now, people can go locally to get stem cell ‘treatments,’’ says Knoepfler, of the University of California, Davis, and Shriners Hospital For Children. “Many people in larger metropolitan areas can just drive 15 minutes to find a clinic offering these kinds of services instead of, say, traveling to Mexico or the Caribbean. I think this reflects a change from what we’ve seen documented in the past and is different from what we typically think about when we think of stem cell tourism.”

Turner and Knoepfler found the businesses through Internet key word searches, text mining, and content analysis of company websites. For each business, the duo recorded the company name, location(s), website addresses, advertised stem cell types, and marketing claims concerning diseases, injuries, and conditions for which stem cells are reportedly administered. Their research should serve as a baseline for future studies of U.S. businesses engaged in direct-to-consumer advertising of purported stem cell interventions.

Key findings from the report include:

  • Clinics advertising stem cell interventions cluster in particular states. They are most likely to be found in California (113 clinics), Florida (104), Texas (71), Colorado (37), Arizona (36), and New York (21).
  • Beverly Hills is home to 18 clinics, more than any other city in the nation, followed by New York (14 clinics), San Antonio (13), Los Angeles (12), Austin (11), Scottsdale (11), and Phoenix (10).
  • Of the stem cell procedures that are marketed, 61% of businesses offer fat-derived stem cell interventions and 48% offer bone-marrow-based treatments. Advertisements for induced pluripotent stem cells (1 business), embryonic stem cells (1 business), and xenogeneic products (2 businesses) are rare.
  • Over 300 of the businesses market interventions for orthopedic issues. Other advertised conditions include pain (150 businesses), sports injuries (90), neurological diseases (80), and immune disorders (75).

“This is a marketplace that is dramatically expanding before our eyes–we were aware early on and tracked it early on, but I don’t think we knew the scope and size of the market,” says Turner, of the Center for Bioethics at the University of Minnesota. “Brakes ought to exist in a marketplace like this, but where are the brakes? Where are the regulatory bodies? And how did this entire industry come into being in a country where stem cell-based interventions and the medical devices that produce them are supposed to be regulated by the FDA?”

Turner and Knoepfler, who runs the popular stem cell blog “The Niche,” grew suspicious of an increase in American stem cell clinics when inquiries from readers and patients changed from Americans asking about going abroad for a stem cell treatment to Americans asking about seeking treatment in the United States. In investigating the people who run these clinics, Turner and Knoepfler found that not only were individuals such as cosmetic surgeons and naturopaths beginning to offer unapproved stem cell interventions, but the “pioneers” in the industry were training others to do the same. It is unclear whether federal authorities–particularly the Food & Drug Administration–and state medical boards missed the scope of the problem or are taking minimal action despite being aware of the spread of such businesses.

“From around 2009 to the present, businesses have been entering the marketplace on a routine basis, they’ve been coming in making marketing assertions about stem cells treating 30-40 different diseases, and no one’s taking meaningful regulatory action,” Turner says. “Does that mean that people are getting access to safe and efficacious interventions or is there basically unapproved human experimentation taking place where people are going to these businesses and receiving experimental investigational cell-based interventions without being given a meaningful account of the lack of knowledge and evidence that they’re being charged for?”

A separate downside is that patients who have unapproved and unproven stem cell interventions decrease their chances of qualifying for FDA-cleared and IRB-approved clinical trials that comply with federal regulations. This is a loss for stem cell research.

“Another serious consideration to think about is that over the years many people have begun to include these businesses in their overall impression of the stem cell field,” Knoepfler says. “There is a real risk that as clinics proliferate, if we don’t address it in a more proactive way, as we see negative outcomes for patients grow and people get mixed bags of information about stem cells, then this could really negatively impact the public perception of this research.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160630135852.htm Original web page at Science Daily

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Our ancestors evolved faster after dinosaur extinction

Our ancestors evolved three times faster in the 10 million years after the extinction of the dinosaurs than in the previous 80 million years, according to UCL researchers.

The team found the speed of evolution of placental mammals — a group that today includes nearly 5000 species including humans — was constant before the extinction event but exploded after, resulting in the varied groups of mammals we see today.

Lead researcher, Dr Thomas Halliday (UCL Genetics, Evolution & Environment), said: “Our ancestors — the early placental mammals – benefitted from the extinction of non-avian dinosaurs and dwindling numbers of competing groups of mammals. Once the pressure was off, placental mammals suddenly evolved rapidly into new forms.

“In particular, we found a group called Laurasiatheria quickly increased their body size and ecological diversity, setting them on a path that would result in a modern group containing mammals as diverse as bats, cats, rhinos, whales, cows, pangolins, shrews and hedgehogs.”

The team found that the last common ancestor for all placental mammals lived in the late Cretaceous period, about three million years before the non-avian dinosaurs became extinct 66 million years ago. This date is 20 million years younger than suggestions from previous studies which used molecular data from living mammals and assumed a near-constant rate of evolution.

In this study, funded by the Natural Environment Research Council and published today in Proceedings B of the Royal Society, the researchers analysed fossils from the Cretaceous to the present day, and used the dates of their occurrence in the fossil record to estimate the timing of divergences based on an updated tree of life. The new tree was released by the same team in 2015 and has the largest representation of Paleocene mammals to date.

The scientists measured all the small changes in the bones and teeth of 904 placental fossils and mapped the anatomical differences between species on the tree of life. From measuring the number of character changes over time for each branch, they found the average rate of evolution for early placental mammals both before and after the dinosaur extinction event. They compared the average rate of evolution over the geological stages before the extinction and the geological stages after to see what impact it had.

Senior author, Professor Anjali Goswami (UCL Genetics, Evolution & Environment and UCL Earth Sciences), said: “Our findings refute those of other studies which overlooked the fossils of placental mammals present around the last mass extinction. Using rigorous methods, we’ve successfully tracked the evolution of early placental mammals and reconstructed how it changed over time. While the rate differed between species, we see a clear and massive spike in the rates of evolution straight after the dinosaurs become extinct, suggesting our ancestors greatly benefitted from the demise of the dinosaurs. The huge impact of the dinosaur extinction on the evolution of our ancestors really shows how important this event was in shaping the modern world.”

Professor Paul Upchurch (UCL Earth Sciences), co-author of the study, added: “Our large and refined data set allows us to build a clearer picture of evolutionary history. We plan on using it to study other large-scale evolutionary patterns such as how early placental mammals dispersed across the continents via land bridges that no longer exist today.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160628221710.htm Original web page at Science Daily

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Cerebrovascular disease linked to Alzheimer’s

Study finds association between diseases in brain blood vessels and dementia. While strokes are known to increase risk for dementia, much less is known about diseases of large and small blood vessels in the brain, separate from stroke, and how they relate to dementia. Diseased blood vessels in the brain itself, which commonly is found in elderly people, may contribute more significantly to Alzheimer’s disease dementia than was previously believed, according to new study results published in June in The Lancet Neurology, a British medical journal.

“Cerebral vessel pathology might be an under-recognized risk factor for Alzheimer’s disease dementia,” the researchers wrote.

The study by researchers from the Rush Alzheimer’s Disease Center analyzed medical and pathologic data on 1,143 older individuals who had donated their brains for research upon their deaths, including 478 (42 percent) with Alzheimer’s disease dementia. Analyses of the brains showed that 445 (39 percent) of study participants had moderate to severe atherosclerosis — plaques in the larger arteries at the base of the brain obstructing blood flow — and 401 (35 percent) had brain arteriolosclerosis — in which there is stiffening or hardening of the smaller artery walls.

The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer’s disease. The increase was 20 to 30 percent for each level of worsening severity. The study also found that atherosclerosis and arteriolosclerosis are associated with lower levels of thinking abilities, including in memory and other thinking skills, and these associations were present in persons with and without dementia.

“Both large and small vessel diseases have effects on dementia and thinking abilities, independently of one another, and independently of the common causes of dementia such as Alzheimer’s pathology and strokes,” said Dr. Zoe Arvanitakis. A neurologist and researcher at the Rush Alzheimer’s Disease Center, Arvanitakis led the study, which was funded by the National Institutes of Health.

Part of Rush University Medical Center, the Rush Alzheimer’s Disease Center is dedicated to the study of Alzheimer’s, a neurological condition that is the most common cause of dementia. It is one of 29 designated centers in the United States funded by the National Institute on Aging.

The study was not designed to determine causation of Alzheimer’s dementia, or even whether vascular disease or Alzheimer’s developed first. “But it does suggest that vessel disease plays a role in dementia,” Arvanitakis said. “We found that blood vessel diseases are very common in the brain, and are associated with dementia that is typically attributed to Alzheimer’s disease during life.”

Does preventing cerebrovascular disease also prevent Alzheimer’s?

The study examined which cognitive difficulties are caused by vessel diseases and whether vessel disease and Alzheimer’s are more destructive in tandem than they would be alone. An editorial in The Lancet Neurology that accompanied the study findings noted that while other studies have indicated that proactive measures like eating a selective diet and getting regular exercise might protect people against getting Alzheimer’s, those interventions might actually be acting on non-Alzheimer’s disease processes, such as cerebrovascular disease.

Arvanitakis says they don’t know yet. “They may decrease actual Alzheimer’s, and possibly even work by yet other pathways,” Arvanitakis said. “We hope to better distinguish how the clinical expression of vessel diseases in the brain differ from those of Alzheimer’s, so that we may eventually use earlier and more targeted treatments for dementia.”

Nearly 47 million people now live with dementia worldwide, according Alzheimer’s Disease International, the international federation of Alzheimer associations around the world. By 2050, that number is projected to be 132 million. Therefore, finding ways to treat or prevent the disease “is a major goal,” Arvanitakis said.

The participants in the study published in Lancet Neurology came from two (RADC) cohort studies, the Religious Orders Study and the Rush Memory and Aging Project, which have followed people older than 65, in their communities, for more than two decades. Participants receive annual health assessments and agree to donate their brains for research upon their deaths. The Lancet Neurology study used clinical data gathered from participants from 1994 to 2015, and pathologic data obtained from examination of the brains donated for autopsy, and used regression analyses to determine the odds of Alzheimer’s dementia and levels of cognitive function, for increasing levels of brain vessel diseases.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160701183319.htm  Original web page at Science Daily

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Electronic nose smells pesticides, nerve gas

The best-known electronic nose is the breathalyser. As drivers breathe into the device, a chemical sensor measures the amount of alcohol in their breath. This chemical reaction is then converted into an electronic signal, allowing the police officer to read off the result. Alcohol is easy to detect, because the chemical reaction is specific and the concentration of the measured gas is fairly high. But many other gases are complex mixtures of molecules in very low concentrations. Building electronic noses to detect them is thus quite a challenge.

Researchers from KU Leuven have now built a very sensitive electronic nose with metal-organic frameworks (MOFs). “MOFs are like microscopic sponges,” postdoctoral researcher Ivo Stassen explains. “They can absorb quite a lot of gas into their minuscule pores.”

“We created a MOF that absorbs the phosphonates found in pesticides and nerve gases. This means you can use it to find traces of chemical weapons such as sarin or to identify the residue of pesticides on food. This MOF is the most sensitive gas sensor to date for these dangerous substances. Our measurements were conducted in cooperation with imec, the Leuven-based nanotechnology research centre. The concentrations we’re dealing with are extremely low: parts per billion — a drop of water in an Olympic swimming pool — and parts per trillion.”

The chemical sensor can easily be integrated into existing electronic devices, Professor Rob Ameloot adds. “You can apply the MOF as a thin film over the surface of, for instance, an electric circuit. Therefore, it’s fairly easy to equip a smartphone with a gas sensor for pesticides and nerve gas.”

“Further research will allow us to examine other applications as well,” Professor Ameloot continues. “MOFs can measure very low concentrations, so we could use them to screen someone’s breath for diseases such as lung cancer and MS in an early stage. Or we could use the signature scent of a product to find out whether food has gone bad or to distinguish imitation wine from the original. This technology, in other words, offers a wide range of perspectives.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160704082706.htm Original web page at Science Daily 

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HPV vaccine reduced cervical abnormalities in young women

Young women who received the human papillomavirus (HPV) vaccine through a school-based program had fewer cervical cell anomalies when screened for cervical cancer, found a new study in CMAJ (Canadian Medical Association Journal).

“Eight years after a school-based HPV vaccination program was initiated in Alberta, 3-dose HPV vaccination has demonstrated early benefits, particularly against high-grade cervical abnormalities, which are more likely to progress to cervical cancer,” writes Dr. Huiming Yang, Medical Officer of Health and Medical Director, Screening Programs, Alberta Health Services, Calgary, Alberta, with coauthors.

Alberta has both a school-based HPV vaccination program and a population-based screening program for cervical cancer. In 2008, the province introduced HPV vaccination for Grade 5 girls (aged 10-11) and a 3-year catch-up program for Grade 9 girls (aged 14-15); in 2014, it was expanded to include boys. The program provides 3 doses of the vaccine that protects against two strains of HPV, which account for 70% of all cases of cervical cancer.

To determine whether HPV vaccination had an impact on Papanicolaou (Pap) test results, Alberta researchers looked at data on the first cohort of women who participated in both the school vaccination program and cervical cancer screening. The 10 204 women in the study population were born between 1994 and 1997 (aged 18 to 21 years) and lived in the province before 2008.

Of the total, 1481 (14.5%) were cases — that is, they had cervical anomalies detected during screening — and the remaining 8723 (85.5%) were controls — with no cervical abnormalities detected. Among cases, most (1384, 93.5%) had low-grade cervical abnormalities, and the remaining 97 (6.5%) had high-grade abnormalities.

More than half of the study participants (56%) were unvaccinated, and 44% had received 1 or more doses of the HPV vaccine before being screened for cervical cancer. Of the women who had been vaccinated, 84% received 3 or more doses. Among the unvaccinated women, 16.1% had cervical abnormalities, compared with 11.8% in the fully vaccinated group.

The authors note that effective HPV vaccination with broad uptake will affect the harms and benefits of cervical screening.

“With population-based HPV vaccination, guidelines for cervical cancer screening may need to include a later age for screening initiation age and/or a longer interval between screenings,” they write.

The authors hope that their findings and future research will lead to improved primary and secondary prevention efforts, with integration of HPV vaccination and cervical cancer screening programs.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160704145722.htm  Original web page at Science Daily

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Infant bodies were ‘prized’ by 19th century anatomists, study suggests

A new study of the University of Cambridge anatomy collection suggests that the bodies of foetuses and babies were a “prized source of knowledge” by British scientists of the 18th and 19th centuries, and were dissected more commonly than previously thought and quite differently to adult cadavers.

Historical research combined with the archaeological assessment of collection specimens shows that foetus and infant cadavers were valued for the study of growth and development, and were often kept in anatomical museums.

Researchers say that socio-cultural factors and changes in the law, as well as the spread of infectious disease during the industrial revolution, dictated the availability of these small bodies for dissection.

The study, conducted by Jenna Dittmar and Piers Mitchell from Cambridge’s Department of Archaeology and Anthropology, is the first to look specifically at how British scientists investigated the changing anatomy of childhood during the 1800s. The findings are published today in the Journal of Anatomy.

The researchers undertook studies of the skeletal collection retained from the former dissecting room of Cambridge’s department of anatomy, with specimen dates ranging from 1768 to 1913.

While the bodies of adults typically underwent a craniotomy — opening of the top of the skull using a saw — the researchers found that anatomists generally kept the skulls of foetuses and young children in one piece. From a total of 54 foetal and infant specimens in the collection, just one had undergone a craniotomy.

Careful study of the bone surface revealed that soft tissues had been gently removed using knives and brushes in order to preserve as much of the bones of the head as possible, although surgical instruments would have been similar to those used on the fully-grown. Tools for other purposes in adults, such as ‘bone nipper’ forceps, were likely used for dividing diminutive ribcages.

The research suggests that anatomists kept the skeletal remains of foetuses and infants for further study and use as teaching aids, whereas adults were frequently reburied after dissection.

“Foetal and infant bodies were clearly valued by anatomists, illustrated by the measures taken to preserve the remains intact and undamaged,” says Dittmar.

“The skulls appear to have been intentionally spared to preserve them for teaching or display. This may explain why so few children with signs of dissection on their bones have been recovered from the burial grounds of hospitals or parish churches, compared with adults.”

Literature from the late 18th century shows that the size of infant bodies made them preferable for certain ‘anatomical preparations’ in teaching, particularly for illuminating the anatomy of the nervous and circulatory systems, which required an entire body to be injected with coloured wax and displayed.

“The valuable and unique knowledge that could only be obtained from the examination of these developing bodies made them essential to the study of anatomy,” says Dittmar.

“During much of the 18th and 19th century, executed criminals provided the main legal access to cadavers, and it was previously thought that dissection of young children was relatively rare. However, changes in the law may have resulted in infant dissections becoming more common.”

The Murder Act in 1752 gave the judiciary power to allow executed murderers — almost entirely men — to be used for medical dissection. These felons hardly made a dent in the growing demand for bodies, and a black market flourished.

Bodies acquired (often grave robbed) by gangs of ‘resurrectionists’, or body-snatchers, were usually sold by the inch, so those of infants were not very profitable, although there are records of ‘smalls’ being traded.

The Anatomy Act of 1832 allowed workhouses and hospitals to donate the bodies of the poor if unclaimed by family, in an attempt to abate the resurrectionists. Infectious diseases such as cholera and tuberculosis were common killers during the industrial revolution, and a major cause of infant death in hospitals and beyond. Workhouses were desperate places, and nearly always lethal to infants.

Until 1838, a legal loophole did not require a stillborn baby to be registered, and a body could be easily sold to an anatomist through an intermediary. But the New Poor Law Amendment Act of 1834 may have had the most significant repercussions of any law for infant material in anatomy collections, say the researchers.

The Act ended parish relief for unmarried women and the availability of assistance from the father of an illegitimate child. Part of Victorian society’s attempt to curtail the illegitimate birth rate, the law succeeded only in contributing to dire situations for poor unwed women, mainly in service positions, who fell pregnant.

“This left very few options for these women: the workhouse, prostitution, abortion and infanticide — all of which were life-threatening,” says Mitchell. By the 1860s, infanticide in England had reached epidemic proportions.

“Our research shows that the major sources of the bodies of very young children were from stillborn babies of destitute mothers, babies who died from infectious diseases, those dying in charitable hospitals, and unmarried mothers who secretly murdered their new-born to avoid the social stigma of single parenthood,” says Mitchell.

“Poor and desperate women at the time of the industrial revolution could not only save the cost of a funeral by passing their child’s body to an anatomist, but also be paid as well. This money would help feed poor families, so the misfortune of one life lost could help their siblings to survive tough times.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160630214457.htm  Original web page at Science Daily

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Exploring ways to ‘coexist with wildlife’

Although protected areas such as national parks can play a crucial role in conserving wildlife, most species of large carnivores and large herbivores also depend on being able to occupy human-dominated landscapes. This sharing of space is often associated with conflicts between humans and wildlife, and between different groups of humans with divergent interests. In order to achieve a situation that can be described as “coexistence” there is a need to develop a more nuanced and realistic understanding of what this state looks like.

A paper written by Neil Carter, assistant professor in the Human-Environment Systems Research Center in the College of Innovation and Design at Boise State, and John Linnell, a senior research scientist at the Norwegian Institute for Nature Research, was recently published in the journal Trends in Ecology and Evolution. Titled “Co-adaptation is key to coexisting with large carnivores,” the paper looks at ways to improve the ability of humans and carnivores to co-exist, which is crucial to carnivore conservation efforts around the world.

The study is based on research conducted by the authors in areas as diverse as North America, Europe and Asia on species such as wolves, tigers, leopards, lynx and bears. In the paper, the researchers note that large carnivores need larger ranges than many protected areas afford. This means that carnivores often come in contact with human populations that are sometimes less than welcoming.

Carter and Linnell wondered what actions could help mitigate the negative impacts of these contacts, allowing both humans and carnivores to more peacefully coexist in shared landscapes. They suggest that mutual adaptations are key to success, implying that not only do wild animals have to behaviourally adapt to the presence of humans, but humans also have to adapt their behavior to the presence of wild animals. Studies conducted by the authors and their colleagues have shown that many species of large carnivores show an incredible ability to occupy heavily modified human-dominated landscapes. Many human societies also show a wide range of adaptations to the proximity of large carnivores. This includes changes to the way they keep livestock and the adoption of cultural or religious practices to “negotiate” their relationship with their wild neighbours.

However, in many areas these adaptations have been lost, either due to a temporary absence of large carnivores or in the face of changing social-economic situations. The result is often severe conflicts of both an economic and social nature. Realising the necessity of adaptation by both humans and the carnivores is a key first step towards transforming conflict to coexistence. Conservation efforts that fail to focus on both halves of the equation are doomed to fail.

A factor for success has to do with realising that a state of coexistence does not involve an idealized absence of conflict. Rather than trying to eliminate all risk, which can mean eliminating a species, the authors explore ways to keep risks below tolerable levels. That involves understanding what factors influence tolerance. While some communities may not tolerate any risks from carnivores, others may tolerate high risks because they attribute carnivores with ecological and cultural benefits that exceed those risks. In many communities, the priorities of various stakeholder groups are still sometimes at odds, and there is a reduced trust in authorities. Interventions such as new policies must take into account local concerns, the authors say, such as the adoption of novel decision-making strategies that give voice to varying viewpoints.

Carter and Linnell believe that the challenges are surmountable through the help of community leaders, conservation organizations, and state or federal agencies. Insights from studies on coexistence “can help reconcile debates about carnivore conservation in shared landscapes and advance broader discourses in conservation,” they wrote, “such as those related to rewilding, novel ecosystems, and land-sharing vs. land-sparing.”

“In many ways large carnivores represent the ultimate test for human willingness to make space for wildlife on a shared planet. If it is possible to find ways to coexist with these species, it should be possible to coexist with any species,” says John Linnell, co-author on the study.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160707083440.htm Original web page at Science Dail

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* Electric assist bikes provide meaningful exercise, cardiovascular benefits for riders

Electric assist bicycles (“pedelecs”) are equipped with a built-in electric motor that provides modest assistance while the rider is actively pedaling, making it easier to cover greater distances and hilly terrain. Pedelecs have steadily grown more popular with consumers over the past decade, especially in Europe and Asia.

While an assist from an electric motor would get a rider disqualified from a competitive cycling competition such as the Tour de France, CU Boulder researchers were interested in studying whether or not pedelecs could help physically inactive non-cyclists achieve recommended daily fitness levels.

To conduct the study, the researchers recruited twenty non-exercising volunteers who were sedentary commuters (car commuters). The researchers tested various aspects of their health, including blood glucose regulation and fitness. The volunteers were then asked to substitute their sedentary commute for riding their pedelec at the speed and intensity of their choice for a minimum of 40 minutes three times per week while wearing a heart monitor and a GPS device.

After a month, the volunteers came back to the lab and had their health tested again. The researchers noticed improvements in the riders’ cardiovascular health, including increased aerobic capacity and improved blood sugar control.

“Commuting with a pedelec can help individuals incorporate physical activity into their day without requiring them to set aside time specifically for exercise,” said James Peterman, a graduate researcher in the Department of Integrative Physiology at CU Boulder and lead author of the new study.

Pedelec bicycles are designed to provide motorized assistance up to speeds of 20 miles per hour. Above that speed, riders must provide all the pedaling power themselves. Based on GPS data, the riders involved in the study rode at an average speed of 12.5 miles per hour and reported no crashes or accidents.

The city of Boulder provided partial funding for the study. Data from the research was provided to the city to assist with the decision on whether or not to allow pedelecs on bike paths.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160707142436.htm  Original web page at Science Daily

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Imaging technique could help focus breast cancer treatment

Cancer Research UK scientists have used imaging techniques as a new way to identify patients who could benefit from certain breast cancer treatments, according to a study published in Oncotarget.

The team at King’s College London, in collaboration with scientists at the CRUK/MRC Oxford Institute for Radiation Oncology, used fluorescence lifetime imaging to confirm if they have joined together.

Fluorescent lifetime imaging is a technique that can accurately measure the distance between two protein molecules. In this study the researchers measured the distance between HER2 and HER3 proteins in breast cancer cells from patients.

The researchers think that patients whose imaging results show that these proteins have bonded together could benefit from HER2 targeted treatment, regardless of whether their tumour has high levels of HER2.

HER2 is a protein which can cause cancer cells to grow. HER2-positive breast cancer cells have high levels of the protein and can be targeted with drugs that block its effects and stop the cancer from growing — drugs being used now include Herceptin and Tykerb. Patients who could benefit from these drugs are identified by testing their cancer cells to see if they show high levels of the HER2 protein.

But this imaging technique, carried out in tumour cells, could pick up additional patients in the future who would respond well to HER2-targeting drugs. It could also confirm which patients may not be suitable for these treatments.

Lead author, Professor Tony Ng, at King’s College London and University College London, said: “This imaging technique could help us pick up patients who might benefit from these drugs but have previously been overlooked.

“Using this test, we should be able to predict which drugs won’t work in patients and avoid prescribing unnecessary treatments — putting the drugs that we’ve got to better use. The next step is to run clinical trials to see if this test could help patients.

“We hope that one day it could not only improve treatment for breast cancer but also for other cancers — including bowel and lung cancer.”

Nell Barrie, senior science information manager at Cancer Research UK, said: “There are more than 50,000 new cases of breast cancer each year but thanks to advances in research, more people survive the disease than ever before. This research could eventually give doctors another way to personalise treatment so that patients receive the drugs that are most likely to help them.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/07/160707172030.htm Original web page at Science Daily

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* Genetic mutation causes ataxia in humans, dogs

Cerebellar ataxia is a condition of the cerebellum that causes an inability to coordinate muscle movements. A study publishing June 16 in Cell Reports now describes a new genetic mutation as an additional cause of ataxia in humans and mice. The mutation, in the gene CAPN1, affects the function of the enzyme calpain-1 and causes abnormal brain development. The same genetic mutation is also associated with ataxia in Parson Russell Terrier dogs.

“There are a number of genes linked to motor function that can be involved in ataxia when mutated,” says Michel Baudry, a neurobiologist at Western University of Health Sciences. “Not only have we identified another, but we’ve also refined our understanding of the calpain enzymes, which is important because several companies have been talking about using calpain inhibitors to treat neurodegenerative diseases.”

Calpain is an enzyme involved with learning, memory, and neurodegeneration in the brain, but it comes in two major forms–calpain-1 and calpain-2. “Nobody could make much progress on figuring out what each form of calpain was doing, because most of the pharmacological studies used molecules that inhibit both types at once” says Baudry. But about eight years ago, Baudry’s team obtained a line of mice genetically engineered to lack only calpain-1 to examine the differences.

Baudry’s mouse studies caught the attention of Henry Houlden, a neurologist at University College London, who was leading a team investigating ataxia. “Around two years ago, we identified two families with CAPN1 mutations with ataxia and spasticity,” Houlden explains. Once the researchers determined that the mutation affected calpain-1’s function, they looked up Baudry’s work on the calpain-1 knockout mice. “Together, we started to investigate the function of this gene,” says Houlden. The current study includes four families with members that have CAPN1 mutations and display symptoms of ataxia.

Baudry’s team started testing whether the knockout mice had ataxia by tracking their balance when placed on a rotating rod. “We had never looked at the cerebellum in our mice before,” says Baudry. “But sure enough, we found that they had mild cerebellar ataxia.”

The researchers demonstrated that during the first week after birth, the mice lacking calpain-1 had a much higher rate of neuronal death in their cerebellum, as compared to normal mice, and many of their synapses failed to mature.

“Calpain-1 is neuroprotective,” explains Baudry. “When the brain matures, excess neurons are supposed to be pruned–but calpain-1 prevents that process from getting out of control.” The team further determined that calpain-1 works normally by degrading an enzyme called PHLPP1, a protein phosphatase involved in programmed cell death. Injecting another compound involved in the pathway during the first postnatal week caused the newborn mice with CAPN1 mutations to develop normally.

Pharmacologically, the attempts to use calpain inhibitors in the clinic may not be working because they don’t discriminate between calpain-1 and calpain-2, says Baudry: “If you want to try to address neurodegeneration, you have to use a calpain-2 inhibitor.” Baudry is currently working with a team to develop calpain-2 inhibitors as neuroprotective drugs, under the umbrella of a new company called NeurAegis.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160616140715.htm Original web page at Science Daily

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* 3-D-printed kidney helps doctors save woman’s organ during complicated tumor removal

Doctors and scientists at Intermountain Medical Center in Salt Lake City printed and used a 3D kidney to help save a patient’s organ during a complicated tumor-removal procedural.

The 3D-printed model allowed doctors to study the patient’s kidney in 3D to determine how to best remove the tumor as it was located in a precarious location adjacent to vital arteries and veins.

Thanks to the 3D-printed model of the organ, doctors were able to maneuver around those sensitive areas and successfully remove the tumor and ultimately save the patient’s kidney.

Linda Green’s case was particularly precarious because her tumor was in the “business section” of the kidney: near an artery, veins and the ureter. It took a multi-disciplinary team, including collaboration between doctors at Intermountain Medical Center and specialists at Intermountain Healthcare’s Transformation Laboratory, to find a solution to her unique medical problem.

Intermountain Medical Center Urological Institute director Jay Bishoff, MD, and radiologist Talmage Shill, MD, prepared CT scans to produce a 3D rendering of Green’s kidney using technology at the Intermountain Transformation Lab, a facility that is the only one of it’s kind in the Intermountain West.

Transformation Lab specialists Cory Smith and Billy Prows worked with Dr. Bishoff and Dr. Shill to render the CT scans for 3D printing. The team rendered and printed the model in two halves, so Dr. Bishoff could examine exactly how the tumor attached to the kidney. This is how he found a small nub that extended up into a pocket where the kidney collects urine.

“Without the 3-D model, the visual images of the CT scans would not have allowed us to identify this nub prior to the surgery,” he said. “The 3D printing technology allowed us to prepare a more complete plan for the patient’s surgery, show the patient the complexities of the procedure and what would be done during surgery to remove the tumor and save the kidney.”

Dr. Bishoff not only used the model to prepare for the surgery, but also brought it into the operating room to reference during the procedure. Through the multi-disciplinary team’s efforts, they managed to remove the tumor and save Green’s kidney.

“I’m just so thankful for everybody at the hospital who was involved and cared,” Green said. Dr. Bishoff was the last of many doctors to examine Green’s case, and she felt “totally confident” in his ability to perform the surgery. “It was like a night-and-day difference, and I completely trust him too. Dr. Bishoff kept me informed and called me personally, which I very much appreciated.”

The Intermountain Healthcare Transformation Lab gathers cutting-edge technologies and assembles creative and experienced personnel to advance healthcare practices.

“We’re giving doctors additional visual tools to see the anatomy in a different way,” Smith said. “In the transformation lab we talk about reimagining imaging — it’s the evolution of imaging.”

The Intermountain Urological Institute tracks urological patient outcomes to determine best practices. The institute is at the forefront of evidence-based and advanced-technological treatment methods.

“While this technology is in its infancy, it is a big step forward in using new technologies like 3D printing to improve patient care,” Dr. Bishoff said.

The institute is based at Intermountain Medical Center, which is the flagship hospital for the Salt Lake City-based Intermountain Healthcare system.

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https://www.sciencedaily.com/releases/2016/06/160624100250.htm  Original web page at Science Daily

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Human brain houses diverse populations of neurons, new research shows

A team of researchers has developed the first scalable method to identify different subtypes of neurons in the human brain. The research lays the groundwork for “mapping” the gene activity in the human brain and could help provide a better understanding of brain functions and disorders, including Alzheimer’s, Parkinson’s, schizophrenia and depression.

By isolating and analyzing the nuclei of individual human brain cells, researchers identified 16 neuronal subtypes in the cerebral cortex — the brain’s outer layer of neural tissue responsible for cognitive functions including memory, attention and decision making. The team, led by researchers at the University of California San Diego, The Scripps Research Institute (TSRI) and Illumina, published their findings in the June 24 online issue of the journal Science.

“We’re providing a unified framework to look at and compare individual neurons, which can help us find out how many unique types of neurons exist,” said Kun Zhang, bioengineering professor at the University of California, San Diego and a corresponding author of the study.

Researchers can use these different neuronal subtypes to build what Zhang calls a “reference map” of the human brain — a foundation to understand the differences between a healthy brain and a diseased brain.

“In the future, patients with brain disorders or abnormalities could be diagnosed and treated based on how they differ from the reference map. This is analogous to what’s being done with the reference human genome map,” Zhang said.

The new study reflects a growing understanding that individual brain cells are unique: they express different types of genes and perform different functions. To better understand this diversity, researchers analyzed more than 3,200 single human neurons in six Brodmann areas, which are regions of the cerebral cortex classified by their functions and arrangements of neurons.

Through an interdisciplinary collaborative effort, the team developed a new method to isolate and sequence individual cell nuclei. TSRI researchers led by neuroscience professor Jerold Chun obtained the samples from a post mortem brain and focused on isolating the neuronal nuclei. Zhang’s lab worked with Fluidigm, a manufacturer of microfluidic chips for single-cell studies, to develop a protocol to identify and quantify RNA molecules in individual neuronal nuclei. Scientists at San Diego-based Illumina sequenced the resulting RNA libraries. Researchers led by biochemistry professor Wei Wang at UC San Diego developed algorithms to cluster and identify 16 neuronal subtypes from the sequenced datasets.

Researchers deciphered what types of genes were “turned on” within each nucleus and revealed that various combinations of the 16 subtypes tended to cluster in cortical layers and Brodmann areas, helping explain why these regions look and function differently.

Neurons exhibited many differences in their transcriptomic profiles — the patterns of genes that are being actively expressed by these cells — revealing single neurons with shared, as well as unique, characteristics that likely lead to difference in cellular function.

“We’re finding new ways to understand the basic building blocks of the brain,” said Blue Lake, a postdoctoral researcher in Zhang’s lab and a co-first author of the study. “Our study opens the door to look at global gene expression patterns and how that defines cell types within a normal tissue, which can also be used to see what’s abnormal in terms of disease or disorders.”

In future studies, researchers aim to analyze neurons in other Brodmann areas of the brain and investigate what subtypes exist in other brain regions. They also plan to study neurons from multiple post mortem human brains (this study only involved one) to investigate neuronal diversity among individuals.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160623150111.htm  Original web page at Science Daily

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* Improving cell transplantation after spinal cord injury: When, where and how?

Spinal cord injuries are mostly caused by trauma, often incurred in road traffic or sporting incidents, often with devastating and irreversible consequences, and unfortunately having a relatively high prevalence (250,000 patients in the USA; 80% of cases are male). One currently explored approach to restoring function after spinal cord injury is the transplantation of olfactory ensheathing cells (OECs) into the damaged area. The hope is that these will encourage the repair of damaged neurons, but does it work? And if so, how can it be optimized?

According to a systematic analysis of the literature published this week in PLOS Biology, after experimental spinal cord injury, transplanting OECs into the site of damage does indeed significantly improve locomotor performance. To reach this conclusion, Ralf Watzlawick, Jan Schwab, and their colleagues at the Ohio State University Wexner Medical Center, Charité Universtaetsmedizin Berlin and the CAMARADES consortium (Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies), analyzed 49 studies, published between 1949 and 2014, which included 62 experiments involving 1164 animals.

Restoration of function after spinal cord injury remains one of the most formidable challenges in regenerative medicine, but cell transplantation into the spinal cord represents a promising treatment strategy. OECs are considered particularly suitable for transplantation because they have been shown to be neuro-protective and to promote neuro-regeneration in different settings, and can be extracted from the patient’s own nasal cavity, thereby minimizing the chances of graft rejection and avoiding the need for immunosuppressive drugs.

However, reports in the literature about the efficacy of transplantation of OECs for treatment of spinal cord injury have been contradictory. Therefore, to investigate the in vivo evidence for the efficacy of this procedure, the authors implemented a systematic review and meta-analysis of the literature. Importantly, the authors set out to explore the potential influence of variations in experimental approaches and unreported data.

“We felt that after more than two decades since the discovery that OECs elicit effects on neural plasticity in vivo, it was time to test their effects by appropriate methodology beyond reproduction,” the authors argued.

The data analysed by the authors justify the use of OECs as a cellular substrate to develop and to optimize minimally invasive and secure protocols for repairing damaged spinal cord. They also identified several aspects of the cell transplantation procedure that could have a significant impact on the size of the therapeutic effect, including: the time-point of application, the use of surgical micro-dissection to “refresh” the scar tissue, the localization of transplanted cells, the number of injections, the injected volume, and the dose of cells administered.

Importantly, by using state-of-the-art statistical methods the authors also found that the impact of publication bias (due to selective failure to report results) was minimal, further supporting the translational potential of this approach.

Despite being focussing on OECs, the findings may be of more general relevance for optimizing the transplantation of other cell types after spinal cord injury.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160531165224.htm  Original web page at Science Daily

 

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Genetic code of red blood cells discovered

Eight days. That’s how long it takes for skin cells to reprogram into red blood cells. Researchers at Lund University in Sweden, together with colleagues at Center of Regenerative Medicine in Barcelona, have successfully identified the four genetic keys that unlock the genetic code of skin cells and reprogram them to start producing red blood cells instead.

“We have performed this experiment on mice, and the preliminary results indicate that it is also possible to reprogram skin cells from humans into red blood cells. One possible application for this technique is to make personalised red blood cells for blood transfusions, but this is still far from becoming a clinical reality,” says Johan Flygare, manager of the research group and in charge of the study.

Every individual has a unique genetic code, which is a complete instruction manual describing exactly how all the cells in the body are formed. This instruction manual is stored in the form of a specific DNA sequence in the cell nucleus. All human cells — brain, muscle, fat, bone and skin cells — have the exact same code. The thing that distinguishes the cells is which chapter of the manual the cells are able to read. The research group in Lund wanted to find out how the cells open the chapter that contains instructions on how to produce red blood cells. The skin cells on which the study was based had access to the instruction manual, but how were the researchers able to get them to open the chapter describing red blood cells?

With the help of a retrovirus, they introduced different combinations of over 60 genes into the skin cells’ genome, until one day they had successfully converted the skin cells into red blood cells. The study is published in the scientific journal Cell Reports.

“This is the first time anyone has ever succeeded in transforming skin cells into red blood cells, which is incredibly exciting,” says Sandra Capellera, doctoral student and lead author of the study.

The study shows that out of 20,000 genes, only four are necessary to reprogram skin cells to start producing red blood cells. Also, all four are necessary in order for it to work.

“It’s a bit like a treasure chest where you have to turn four separate keys simultaneously in order for the chest to open,” explains Sandra.

The discovery is significant from several aspects. Partly from a biological point of view — understanding how red blood cells are produced and which genetic instructions they require — but also from a therapeutic point of view, as it creates an opportunity to produce red blood cells from the skin cells of a patient. There is currently a lack of blood donors for, for instance, patients with anemic diseases. Johan Flygare explains:

“An aging population means more blood transfusions in the future. There will also be an increasing amount of people coming from other countries with rare blood types, which means that we will not always have blood to offer them.”

Red blood cells are the most common cells in the human body, and are necessary in order to transport oxygen and carbon dioxide. Millions of people worldwide suffer from anemia — a condition in which the patient has an insufficient amount of red blood cells. Patients with chronic anemia are among the most problematic cases. They receive regular blood transfusions from different donors, which can eventually lead to the patient developing a reaction to the new blood. They simply become allergic to the donor’s blood. Finding a feasible way to make blood from an individual’s own skin cells would bring relief to this group of patients. However, further studies on how the generated blood performs in living organisms are needed.

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https://www.sciencedaily.com/releases/2016/06/160602132638.htm Original web page at Science Daily

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From a heart in a backpack to a heart transplant

All transplant patients are exceptional, but Stan Larkin’s successful heart transplant comes after living more than a year without a human heart and relying on a heart device he carried in a backpack.

The first patient in Michigan ever discharged with a SynCardia temporary total artificial heart in 2014, Larkin was back at the University of Michigan Frankel Cardiovascular Center in May for a heart transplant.

The surgery performed by Jonathan Haft, M.D., was a unique national triumph in efforts to replace the failing heart as heart disease grows and donor hearts remain scarce.

“It was an emotional rollercoaster,” Larkin, 25, said at a news conference when he described living with the total artificial heart that was implanted to keep him alive until a donor heart became available.

“I got the transplant two weeks ago and I feel like I could take a jog as we speak. I want to thank the donor who gave themselves for me. I’d like to meet their family one day. Hopefully they’d want to meet me.”

Stan’s older brother Dominique also relied on a TAH before a heart transplant in 2015. The brothers were diagnosed as teenagers with familial cardiomyopathy, a type of heart failure that can strike seemingly healthy people without warning. It’s linked to a leading cause of sudden death among athletes.

“They were both very, very ill when we first met them in our intensive care units,” says Haft, associate professor of cardiac surgery. “We wanted to get them heart transplants, but we didn’t think we had enough time. There’s just something about their unique anatomic situation where other technology wasn’t going to work.”

The temporary total artificial heart is used when both sides of the heart fail, and more common heart-supporting devices are not adequate to keep patients alive.

Rather than stay in the hospital, Larkin used a wearable, 13.5 pound Freedom® portable driver to keep the artificial heart going.

“He really thrived on the device,” Haft said looking at a photo of Stan on a basketball court. “This wasn’t made for pick-up basketball,” he joked.

As Haft teaches at the University of Michigan Medical School, the brothers have joined him to share the impact that circulatory support can have on those with end-stage heart failure.

Of the 5.7 million Americans living with heart failure, about 10 percent have advanced heart failure, according to the American Heart Association.

“You’re heroes to all of us,” says David J. Pinsky, M.D., a director of the U-M Frankel Cardiovascular Center. “The fact that you take your story public and allow us to teach others makes a difference. You’ll make a difference for a lot of patients. You’ll make a difference to the doctors of the future. We thank you for allowing us to share your story and your bravery in sharing it.”

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https://www.sciencedaily.com/releases/2016/06/160603072131.htm Original web page at Science Daily

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* New drug clears psoriasis in clinical trials

About 80 percent of patients with moderate to severe psoriasis saw their disease completely or almost completely cleared with a new drug called ixekizumab, according to three large, long-term clinical trials led by Northwestern Medicine.

The results of these phase III trials were compiled in a paper published in the New England Journal of Medicine.

“This group of studies not only shows very high and consistent levels of safety and efficacy, but also that the great majority of the responses persist at least 60 weeks,” said Dr. Kenneth Gordon, a professor of dermatology at Northwestern University Feinberg School of Medicine and first author of the paper.

Affecting about 3 percent of the world’s population, psoriasis is an immune-mediated inflammatory disease that causes itchy, dry and red skin. It is also associated with an increased risk for depression, heart disease and diabetes, among other conditions.

Ixekizumab works by neutralizing a pathway in the immune system known to promote psoriasis.

To test the drug’s efficacy over time — and to help clinicians determine whether its benefits outweigh any risks — the three studies enrolled a total of 3,736 adult patients at more than 100 study sites in 21 countries. All participants had moderate to severe psoriasis, which is defined as covering 10 percent or more of the body. Patients were randomly assigned to receive injections of ixekizumab at various doses or a placebo over a period of more than a year.

The investigators assessed whether the drug reduced the severity of psoriasis symptoms compared to the placebo and evaluated safety by monitoring adverse events. By the 12th week, 76.4 to 81.8 percent of patients has their psoriasis classified as “clear” or “minimal” compared to 3.2% of patients on the placebo. By the 60th week, 68.7 to 78.3 percent of patients had maintained their improvement.

“Based on these findings, we expect that 80 percent of patients will have an extremely high response rate to ixekizumab, and about 40 percent will be completely cleared of psoriasis,” Gordon said. “Ten years ago, we thought complete clearance of this disease was impossible. It wasn’t something we would even try to do. Now with this drug, we’re obtaining response levels higher than ever seen before.”

Adverse events associated with ixekizumab included slightly higher rates of neutropenia (low white blood cell count), yeast infection and inflammatory bowel disease compared to the placebo. The safety of therapy longer than 60 weeks will need to be monitored in the future.

The drug has been approved by the Food and Drug Administration since the trials were completed.

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https://www.sciencedaily.com/releases/2016/06/160609174808.htm Original web page at Science Daily

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A new way to nip AIDS in the bud

Now, University of Utah researchers found a way to turn protease into a double-edged sword: They showed that if they delay the budding of new HIV particles, protease itself will destroy the virus instead of helping it spread. They say that might lead, in about a decade, to new kinds of AIDS drugs with fewer side effects.

“We could use the power of the protease itself to destroy the virus,” says virologist Saveez Saffarian, an associate professor of physics and astronomy at the University of Utah and senior author of the study released today by PLOS Pathogens, an online journal published by the Public Library of Science.

So-called cocktails or mixtures of protease inhibitors emerged in the 1990s and turned acquired immune deficiency syndrome into a chronic, manageable disease for people who can afford the medicines. But side effects include fat redistribution in the body, diarrhea, nausea, rash, stomach pain, liver toxicity, headache, diabetes and fever.

“They have secondary effects that hurt patients,” says Mourad Bendjennat, a research assistant professor of physics and astronomy and the study’s first author. “And the virus becomes resistant to the inhibitors. That’s why they use cocktails.”

Bendjennat adds that by discovering the molecular mechanism in which protease interacts with HIV, “we are developing a new approach that we believe may be very efficient in treating the spread of HIV.”

However, he and Saffarian emphasize the research is basic, and that it will be a decade before more research might develop the approach into news AIDS treatments.

Inside a cell infected by HIV, new virus particles are constructed largely with a protein named Gag. Protease enzymes are incorporated into new viral particles as they are built, and are thought to be activated after the new particles “bud” out of infected cell and then break off from it.

The particles start to bud from the host cell in a saclike container called a vesicle, the neck of which eventually separates from the outer membrane of the infected cell. “Once the particles are released, the proteases are activated and the particles transform into mature HIV, which is infectious,” Saffarian says.

“There is an internal mechanism that dictates activation of the protease, which is not well understood,” he adds. “We found that if we slow the budding process, the protease activates while the HIV particle is still connected to the outer membrane of host infected cell. As a result, it chews out all the proteins inside the budding HIV particle, and those essential enzymes and proteins leak back into the host cell. The particle continues to bud out and release from the cell, but it is not infectious anymore because it doesn’t have the enzymes it needs to mature.”

The scientists found they could slow HIV particles from budding out of cells by interfering with how they interact with proteins named ESCRTs (pronounced “escorts”), or “endosomal sorting complexes required for transport.”

ESCRTs are involved in helping pinch off budding HIV particles — essentially cutting them from the infected host cell.

Saffarian says scientific dogma long has held “that messing up the interactions of the virus with ESCRTs results in budding HIV particles permanently getting stuck on the host cell membrane instead of releasing.” Bendjennat says several studies in recent years indicated that the particles do get released, casting some doubt on the long held dogma.

The new study’s significance “is about the molecular mechanism: When the ESCRT machinery is altered, there is production of viruslike particles that are noninfectious,” he says. “This study explains the molecular mechanism of that.”

“We found HIV still releases even when early ESCRT interactions are intentionally compromised, however, with a delay,” Saffarian says. “They are stuck for a while and then they release. And by being stuck for a while, they lose their internal enzymes due to early protease activation and lose their infectivity.”

Bendjennat says by delaying virus budding and speeding “when the protease gets activated, we are now capable of using it to make new released viruses noninfectious”

The experiments used human skin cells grown in tissue culture. It already was known that new HIV particles assemble the same way whether the infected host cell is a skin cell, certain other cells or the T-cell white blood cell infected by the virus to cause AIDS. The experiments involved both live HIV and so-called viruslike particles.

Bendjennat and Saffarian genetically engineered mutant Gag proteins. A single HIV particle is made of some 2,000 Gag proteins and 120 copies of proteins known as Gag-Pol, as well as genetic information in the form of RNA. Pol includes protease, reverse transcriptase and integrase — the proteins HIV uses to replicate.

The mutant Gag proteins were designed to interact abnormally with two different ESCRT proteins, named ALIX and Tsg101.

When the researchers interfered with ALIX, release was delayed 75 minutes, reducing by half the infectivity of the new virus particle. When the scientists interfered with Tsg101, release was delayed 10 hours and new HIV particles were not infectious.

The scientists also showed that how fast an HIV particle releases from an infected cell depends on how much enzyme cargo it carries in the form of Pol proteins. By interfering with ESCRT proteins during virus-release experiments with viruslike particles made only of Gag protein but none of the normal Pol enzymes, the 75-minute delay shrank to only 20 minutes, and the 10-hour delay shrank to only 50 minutes.

“When the cargo is large, the virus particle needs more help from the ESCRTs to release on a timely fashion,” Saffarian says.

Because HIV carries a large cargo, it depends on ESCRTs to release from an infected cell, so ESCRTs are good targets for drugs to delay release and let HIV proteases leak back into the host cell, making new HIV particles noninfectious, he says.

Bendjennat says other researchers already are looking for drugs to block ESCRT proteins in a way that would prevent the “neck” of the budding HIV particle from pinching off or closing, thus keeping it connected to the infected cell. But he says the same ESCRTs are needed for cell survival, so such drugs would be toxic.

Instead, the new study suggests the right approach is to use low-potency ESCRT-inhibiting drugs that delay HIV release instead of blocking it, rendering it noninfectious with fewer toxic side effects, he adds.

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https://www.sciencedaily.com/releases/2016/06/160609150828.htm  Original web page at

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Diet lacking in zinc is detrimental to human, animal health

The trace element zinc has an impact on the essential metabolic functions of most living organisms. New research carried out by the Chair of Animal Nutrition at the Technical University of Munich (TUM) has found that even minimal zinc deficiency impairs digestion, albeit without any typical symptoms such as skin problems or fatigue. Hence, short-term zinc deficiency in the diet should be avoided.

The test series established that even slight zinc deficiency in an animal’s diet impedes pancreatic digestive activity and results in significant digestive impairment, even at an early stage. The study undertaken by Daniel Brugger of the Chair of Animal Nutrition at TUM was recently published in the British Journal of Nutrition.

Scientist Brugger charted a new path since all previous studies had compared the functions of animals with clinical zinc deficiency to those of animals that had adequate amounts of this trace element in their bodies. “It is important to note that, in nature, clinical zinc deficiency does not really occur, neither in animals nor in humans,” explains lead author Brugger. Hence, Brugger carried out his study on animals with short-term or subclinical zinc deficiency. As the trace element only exists in small amounts in an organism, it has to be consumed by way of nutrition. In piglets, for instance, a clinical or manifest zinc deficiency can — under feeding conditions applied in practice — only be achieved after about ten days, explains the TUM scientist. This is why he ended his test series early, after just eight days.

The unnoticed start of zinc depletion occurs without any visible symptoms, but minute changes can be identified in the liver and in the blood. For the purpose of this study, piglets which had just been weaned were fed a diet containing different amounts of zinc to develop early-stage zinc deficiency. This was the only way for the scientists to trace and analyze what effects dwindling zinc deposits would have on the animals’ metabolisms. On one hand, it was observed that the body tried to absorb zinc more efficiently, while on the other, it reduced pancreatic zinc excretion. Since clinical zinc deficiency reduces the test animals’ appetite, “various hypotheses were derived, for example, that zinc deficiency had a direct impact on the vagus nerve. The real reason, however, may be much simpler: the accumulation of undigested food inside the gastrointestinal tract due to zinc deficiency results in feeling less hungry,” says Brugger.

The pancreas is the control center for food digestion and energy homeostasis in the body. It pumps zinc into the gastrointestinal tract in order to maintain a consistent zinc level. Conversely, if an organism is depleted of zinc, it reduces its pancreatic zinc excretion to a minimum. The starting point for Daniel Brugger’s study was the hypothesis that this mechanism may be related to digestion.

Feed digestion is of enormous importance for growing livestock and especially the first few weeks after young animals are weaned from their mothers are of crucial importance. This is a factor that must not be underestimated by farmers.

“We proved that there is a direct correlation between the amount of digestive enzymes inside the pancreas and zinc levels in the organism as a whole,” explains Brugger. “Even short intervals of zinc deficiency in the diet should therefore be avoided. Given the similarities between a pig’s organism and the human organism, we may draw the following conclusion when applying our results to the human body: an egg or two more once in a while can do no harm.” Brugger advises vegans, vegetarians and older people to monitor their zinc intake. Among other things, a subclinical zinc deficiency in humans has been attributed to increased levels of inflammation markers and reduced immunocompetence.

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https://www.sciencedaily.com/releases/2016/06/160609115127.htm Original web page at Science Daily

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Antibody-based drug helps ‘bridge’ leukemia patients to curative treatmen

In a randomized Phase III study of the drug inotuzumab ozogamicin, a statistically significant percentage of patients with acute lymphoblastic leukemia (ALL) whose disease had relapsed following standard therapies, qualified for stem cell transplants.

Inotuzumab ozogamicin, also known as CMC-544, links an antibody that targets CD22, a protein found on the surface of more than 90 percent of ALL cells. Once the drug connects to CD22, the ALL cell draws it inside and dies.

The study, which revealed complete remission rates of nearly 81 percent and significantly longer progression-free and higher overall survival rates than with standard therapies, was conducted at The University of Texas MD Anderson Cancer Center. Study findings were reported in the June 12 online issue of the New England Journal of Medicine.

“Forty-one percent of ALL patients in the study were able to proceed to transplant after receiving inotuzumab ozogamicin compared with the 11 percent we have seen qualify through standard chemotherapy,” said Hagop Kantarjian, M.D., chair of Leukemia. “Given that stem cell transplant is considered the only curative treatment option, the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging.”

Donor stem cell transplants generally are considered curative for this aggressive form of leukemia with more than 6,500 American adults expected to be diagnosed with the disease in 2016. However, patients must be in complete remission before they are eligible for transplant.

Current therapies for adults with newly diagnosed B-cell ALL result in complete remission rates (CR) of 60 to 90 percent. However, many of those patients will relapse and only about 30 to 50 percent will achieve long-term, disease-free survival lasting more than three years.

“Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier, and just 18 to 25 percent in those who relapse later,” said Kantarjian. “Patients in the inotuzumab ozogamicin study had remission rates of 58 percent, higher than previously reported, possibly due to patients being treated later in the disease course.”

The study reported moderate side effects, the most common being cytopenia, a disorder that reduces blood cell production, and liver toxicity. Funding was provided by Pfizer, Inc.

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https://www.sciencedaily.com/releases/2016/06/160612105823.htm Original web page at Science Daily

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* World’s first vaccine developed against Toxic Shock Syndrome

Toxic Shock Syndrome (TSS) is a severe circulatory and organ failure caused by bacterial toxins, usually triggered by bacteria from the Staphylococcus group. Researchers from MedUni Vienna’s Department of Clinical Pharmacology, in collaboration with the company Biomedizinische Forschungsgesellschaft mbH in Vienna, have now developed the world’s first safe and effective vaccine against this disease and successfully tested it in a Phase I trial. The promising results were recently published in the leading journal “The Lancet Infectious Diseases.”

This syndrome was first described in the 1980s. General symptoms of sepsis or blood poisoning occurred in young women who had used so-called “super tampons” during their periods. This is why the syndrome was also known as “tampon disease.” This subsequently led to the absorption capacity of tampons being regulated.

Staphylococci colonize nearly all of us, especially on our skin and mucous membranes. They are totally harmless to most people. “However, for people with weakened immune systems, they can cause serious diseases such as Toxic Shocks Syndrome,” explains Martha Eibl, director of Biomedizinische Forschungsgesellscaft mbH and former university professor at the Institute for Immunology of the medical faculty of the University of Vienna. This affects dialysis patients, the chronically sick, people with liver diseases and people recovering after heart operations. “Nevertheless, in 50% of cases the disease is associated with menstruation in young women,” says Bernd Jilma from MedUni Vienna’s Department of Clinical Pharmacology.

The vaccine, which has now been found to be safe and effective — and to have practically no side effects — in a clinical Phase I trial, and has been tested on 46 young men and women, was developed from a detoxified Staphylococcus toxin. The vaccine is injected into the skin and its effect is similar to that of a tetanus vaccination, says Jilma. “Immunization with such vaccines lasts for five years or more.” Once vaccinated, a person develops antibodies, which become active if the germs start to pose a threat. A blood test can show whether someone is short of antibodies. Risk groups could then be preventively vaccinated.

“We are well on the way to having a vaccine that prevents this series disease. However, it will still take some years before it is in clinical use,” explains Eibl. A Phase II trial with a larger test population has now started, in order to check the initial, promising results. “We are still looking for more volunteers,” says Jilma.

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https://www.sciencedaily.com/releases/2016/06/160611125403.htm Original web page at Science Daily

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Neurologic symptoms common in early HIV infection

A team led by researchers from UCSF and Yale has found that half of people newly infected with HIV experience neurologic issues. These neurologic findings are generally not severe and usually resolve after participants started anti-retroviral therapy.

“We were surprised that neurologic findings were so pervasive in participants diagnosed with very recent HIV infection,” said study lead author, Joanna Hellmuth, MD, MHS, clinical fellow in UCSF’s Department of Neurology. “While the findings were mild, it is clear that HIV affects the nervous system within days of infection. Since the majority of these neurologic issues were resolved with treatment, our study reinforces recommendations that people at risk for HIV test often and start antiretroviral treatment immediately if they are infected.”

The research will be published in the June 10, 2016, issue of Neurology, the medical journal of the American Academy of Neurology.

The team examined 139 participants in the RV254 Thai cohort who were recently infected with HIV. The time from infection to entry into the study ranged from 3 to 56 days with a median of 19 days. At this stage, participants would not test positive on the common antibody tests for HIV since they have not been infected long enough for a robust specific immune response to take place. Fifty-three percent had neurologic findings, with a third experiencing cognitive deficits, a quarter having motor issues, and nearly 20 percent experiencing neuropathy. Many experienced more than one symptom. One participant was diagnosed with Guillain-Barré Syndrome, the only severe case found in the cohort.

“In the early days of the epidemic in San Francisco, approximately 10 percent of patients with recent HIV infection presented with dramatic neurological disease. But that was likely due to patients coming in early because of the severity of symptoms they were experiencing. The Thai cohort has given us an opportunity to look at a broad range of newly infected patients, analyze their neurological functioning systematically and follow them over time. We are gaining deeper insights into the degree to which early HIV affects the nervous system,” said study senior author, Serena Spudich, MD, Yale associate professor of neurology.

All participants were offered and commenced antiretroviral treatment at diagnosis. Ninety percent of the issues present at diagnosis were resolved after one month of treatment, but 9 percent of the participants had neurologic symptoms that were still not resolved six months after starting therapy. In addition, neurological symptoms were associated with higher levels of HIV found in participants’ blood.

The study participants underwent extensive neurologic assessments. Self reported symptoms were correlated with objective neuropsychological testing. In addition, a quarter of participants opted to undergo a lumbar puncture and almost half of the patients agreed to undergo a MRI.

“This is one of the first comprehensive studies scrutinizing the involvement of the nervous system in early infection. Since we have been able to maintain the cohort for five years now, we will be able to study whether there are any persistent abnormalities that need to be addressed. Additionally, the ubiquity of symptoms in early infection found in this study reinforces the need for the brain to be considered as a compartment containing latent HIV as we design cure studies,” said study co-author, Victor Valcour, MD, PhD, UCSF professor of neurology.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/06/160613105753.htm Original web page at Science Daily

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* Fighting cancer with the help of someone else’s immune cells

A new step in cancer immunotherapy: researchers from the Netherlands Cancer Institute and University of Oslo/Oslo University Hospital show that even if one’s own immune cells cannot recognize and fight their tumors, someone else’s immune cells might. Their proof of principle study is published in the journal Science on May 19th.

The study shows that adding mutated DNA from cancer cells into immune stimulating cells from healthy donors create an immune response in the healthy immune cells. Inserting the targeted components from the donor immune cells back into the immune cells of the cancer patients, the researchers were able to make cancer patients’ own immune cells recognize cancer cells.

The extremely rapidly developing field of cancer immunotherapy aims to create technologies that help the body’s own immune system to fight cancer. There are a number of possible causes that can prevent the immune system from controlling cancer cells. First, the activity of immune cells is controlled by many ‘brakes’ that can interfere with their function, and therapies that inactivate these brakes are now being tested in many human cancers. As a second reason, in some patients the immune system may not recognize the cancer cells as aberrant in the first place. As such, helping the immune system to better recognize cancer cells is one of the main focuses in cancer immunotherapy.

Ton Schumacher of the Netherlands Cancer Institute and Johanna Olweus of the University of Oslo and Oslo University Hospital decided to test whether a ‘borrowed immune system’ could “see” the cancer cells of the patient as aberrant. The recognition of aberrant cells is carried out by immune cells called T cells. All T cells in our body scan the surface of other cells, including cancer cells, to check whether they display any protein fragments on their surface that should not be there. Upon recognition of such foreign protein fragments, T cells kill the aberrant cells. As cancer cells harbor faulty proteins, they can also display foreign protein fragments — also known as neo-antigens — on their surface, much in the way virus-infected cells express fragments of viral proteins.

To address whether the T cells of a patient react to all the foreign protein fragments on cancer cells, the research teams first mapped all possible neo-antigens on the surface of melanoma cells from three different patients. In all 3 patients, the cancer cells seemed to display a large number of different neo-antigens. But when the researchers tried to match these to the T cells derived from within the patient’s tumors, most of these aberrant protein fragments on the tumor cells went unnoticed.

Next, they tested whether the same neo-antigens could be seen by T-cells derived from healthy volunteers. Strikingly, these donor-derived T cells could detect a significant number of neo-antigens that had not been seen by the patients’ T cells.

“In a way, our findings show that the immune response in cancer patients can be strengthened; there is more on the cancer cells that makes them foreign that we can exploit. One way we consider doing this is finding the right donor T cells to match these neo-antigens.,” says Ton Schumacher. “The receptor that is used by these donor T-cells can then be used to genetically modify the patient’s own T cells so these will be able to detect the cancer cells.”

“Our study shows that the principle of outsourcing cancer immunity to a donor is sound. However, more work needs to be done before patients can benefit from this discovery. Thus, we need to find ways to enhance the throughput. We are currently exploring high-throughput methods to identify the neo-antigens that the T cells can “see” on the cancer and isolate the responding cells. But the results showing that we can obtain cancer-specific immunity from the blood of healthy individuals are already very promising,” says Johanna Olweus.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160519144556.htm  Original web page at Science Daily

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Why women earn less: Just two factors explain post-PhD pay gap

Women earn nearly one-third less than men within a year of completing a PhD in a science, technology, engineering or mathematics (STEM) field, suggests an analysis of roughly 1,200 US graduates.

Much of the pay gap, the study found, came down to a tendency for women to graduate in less-lucrative academic fields — such as biology and chemistry, which are known to lead to lower post-PhD earnings than comparatively industry-friendly fields, such as engineering and mathematics.

But after controlling for differences in academic field, the researchers found that women still lagged men by 11% in first-year earnings. That difference, they say, was explained entirely by the finding that married women with children earned less than men. Married men with children, on the other hand, saw no disadvantage in earnings.

Many studies have reported similar gender pay gaps and have identified similar contributing factors — but few have systematically broken down the relative contributions of different variables, says Bruce Weinberg, an economist at the Ohio State University in Columbus who led the study, published in the May issue of American Economic Review. “I was quite surprised that we could explain the wage gap using just field of study and family structure,” he says.

An unmarried, childless woman earned — on average — the same annual salary after receiving her doctorate as a man with a PhD in the same field, the researchers found. The study examined the employment and earnings of 867 men and 370 women who graduated between 2007 and 2010 from 4 different universities.

Weinberg says that the data cannot identify or tease apart factors that might explain why married women with children earn less — among the possibilities, whether employers assign different responsibilities and salaries to these women, or whether the women spend less time or energy on their careers. But, he says, “our data suggest that these positions, as they are currently structured and operate, are not fully family-friendly for women”.

The findings support earlier research that suggests that parental and household responsibilities often affect women disproportionately, particularly in environments without adequate work–life and family policies, says Heather Metcalf, director of research and analysis for the US Association for Women in Science (AWIS) in Alexandria, Virginia.

The analysis is part of the UMETRICS project, based at the University of Michigan in Ann Arbor, which links anonymized census data on employment and income to student information from a consortium of universities, mainly in the midwestern United States.

Mary Ann Mason, a law professor at the University of California, Berkeley, says that the work is a “good, careful study”, albeit limited in that it cannot yet provide information on what happened in later postdoc years. Research by Mason and others suggests that women who have young children within 5–10 years after earning their PhDs are less likely to have tenure-track jobs or to hold tenured faculty positions than men or women without children, for instance.

An important missing piece, says economist Shulamit Kahn at Boston University in Massachusetts, is whether the women and men in the study worked equal numbers of hours. Kahn’s research suggests that, outside of academia, female scientists tend to work slightly fewer hours than do their male counterparts. (That paper did not examine scientists’ family status).

Weinberg says that the team is working to expand and extend the project, first by securing participation from more universities. He hopes, eventually, to be able to track doctoral recipients over the first 5–10 years of their post-PhD careers.

Nature doi:10.1038/nature.2016.19950

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/why-women-earn-less-just-two-factors-explain-post-phd-pay-gap-1.19950 Original web page at Nature

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Changes in ‘microbiome’ during canine atopic dermatitis could lead to antibiotic-free therapies for human, canine disease

Atopic dermatitis (AD), a chronic inflammatory skin condition and the most common form of eczema, is estimated to afflict as much as 10 percent of the U.S. population, and is much more common now than it was 50 years ago. Veterinary clinical estimates also show that approximately 10 percent of dogs have atopic dermatitis. How AD arises isn’t yet fully understood, but a new study from researchers from the Perelman School of Medicine at the University of Pennsylvania and Penn’s School of Veterinary Medicine, have uncovered important insights about the association of AD in dogs compared to humans. The study appears online in the Journal of Investigative Dermatology.

To a greater extent than mouse models, canine AD shares important features of the human version. For example, in both humans and dogs AD has been linked to abnormal blooms of Staphyloccocus bacteria on the skin — mostly Staphyloccocus aureus in humans, and Staphyloccocus pseudintermedius in dogs.

In the study, the research team, comprised of veterinary dermatologists, microbiologists, pathologists, and primary scientists, tracked the bacterial populations, or “microbiomes,” on dogs’ skin, and key properties of the skin’s barrier function during an occurrence of AD, and again after standard treatment with antibiotics. During the flare, researchers observed a sharp decrease in the diversity of the skin bacterial population as certain bacterial species proliferated, along with a decrease in the skin’s protective barrier. With antibiotic therapy, both measures returned to normal levels.

“In both canine and human atopic dermatitis we hypothesize there is a similar relationship among skin barrier function, the immune system, and microbes, even if the individual microbe species aren’t identical,” said senior author Elizabeth A. Grice, PhD, an assistant professor of Dermatology and Microbiology at the Perelman School of Medicine at the University of Pennsylvania. “The hope is that insights gained from this study and others like it will enable us one day to treat this condition by altering the skin’s microbiome without antibiotics.”

Thirty-two dogs (15 with canine AD, and 17 without) from Penn Vet’s Ryan Hospital were enrolled in the study. On three occasions — first during AD flares in the affected dogs, then after 4-6 weeks of targeted antibiotics, and finally 4-6 weeks after treatment concluded — the team took swabs from several areas of skin on the affected dogs. They surveyed the microbiomes of these samples by amplifying and sequencing copies of a key bacterial gene whose DNA sequence is distinct for different bacterial species.

Samples from the dogs with ongoing AD had almost ten times the proportion of Staphylococcus species, compared to the control dogs. Corynebacterium species also rose, as they typically do in humans with AD. A standard measure of the diversity of the dogs’ skin microbiomes also decreased sharply, indicating that the abnormal bacterial proliferation — chiefly from S. pseudintermedius — had crowded out other, harmless or potentially beneficial bacterial species.

At the second visit, immediately following completion of antibiotic therapy, the abundance of Staphyloccocus and Corynebacterium on the skin of affected dogs and the diversity of their skin microbiome had returned almost to the levels seen in the control dogs. Those measures remained largely the same in the third visit, after antibiotic therapy was finished.

Impairment in the skin’s ability to work as a “barrier” to keep moisture in and harmful bacteria out is considered a possible factor in triggering or advancing AD. Under the guidance of Elizabeth Mauldin, DVM DACVP, DACVD, an associate professor of Dermatopathology in Penn’s School of Veterinary Medicine, the researchers also tested skin barrier function in the dogs at each of their three visits. Results showed that the low-bacterial-diversity state of AD flares — corresponding to lesions of AD on the skin — correlated with impairments in the skin barrier, as indicated by a standard test of the water loss rate through the skin (TEWL).

“We don’t know if the bacterial overgrowth is weakening the skin’s barrier function or a weakening of the barrier is enabling the bacterial overgrowth, but we do know now that they’re correlated, and that’s a novel finding,” Grice said.

The research team is now conducting further studies of the microbiome in canine atopic dermatitis, in particular to determine how antimicrobial therapy promotes bacterial resistance.

“This investigation is a prime example of the One Health approach to research, a recognition that we’re dealing with the same disease processes in animals and in humans,” said lead author Charles Bradley, VMD, DACVP, a lecturer and dermatopathologist of pathobiology in Penn’s School of Veterinary Medicine. “The findings highlight the importance of dogs as a model for human dermatitis and help lay the groundwork for new therapeutic strategies, for example involving microbiome transplants to compete with the harmful bacterial overgrowth, as an alternative to antibiotic therapy.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/04/160425192814.htm  Original web page at Science Daily

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* Hormones that are released during hunger affect decision making

Never make a decision when you are hungry. The hormone ghrelin — that is released before meals and known to increase appetite — has a negative effect on both decision making and impulse control. Such were the results of a recently conducted study at Sahlgrenska University.

When hungry, the hormone ghrelin is produced in the stomach. In a new study conducted on rats at Sahlgrenska Academy, University of Gothenburg, the hormone has been shown to have a negative effect on decision making capabilities and impulse control.

“For the first time, we have been able to show that increasing ghrelin to levels that are seen prior to meals or during fasting, causes the brain to act impulsively and also affects the ability to make rational decisions,” says Karolina Skibicka, docent at Sahlgrenska Academy, University of Gothenburg.

Impulsivity is complex, but can be broken down into impulsive action (inability to resist a motoric response) and impulsive choice (inability to delay gratification).

Many have experienced the difficulty of resisting getting a sandwich or something else, even if we know that dinner will be served soon, and the same is true for the rats used in the study.

The rats can be trained to be rewarded (with sugar) when they execute an action such as pressing a lever (“go”) — or instead they can be rewarded only when they resist pressing the lever (“no-go”) when an appropriate learned signal is given. They learn this by repeatedly being given a signal, for example, a flash of light or a buzzing sound that tells them which action should be executed for them to receive their reward.

An inability to resist pressing the lever, when the “no-go” signal is given, is a sign of impulsivity. Researchers found that rats given ghrelin directly into the brain, which mimics how the stomach would notify us of a need to eat, were more likely to press the lever instead of waiting, despite it causing them loose their reward.

The ability to delay gratification in order to get a greater reward later is a comparable measure of impulsive choice (decision). It can be illustrated by options such as those between getting a single cookie now or several cookies if you wait a few minutes, or overeating high-calorie foods for immediate feeling of pleasure while disregarding the long term benefits of eating less or eating healthy.

The person who chooses immediate gratification even though waiting provides a greater reward, is characterized as being more impulsive and that implies a poorer ability to make rational decisions.

Researchers at Sahlgrenska Academy found that higher levels of ghrelin prevented the rats from being able to wait for the greater reward. They further evaluated where in the brain ghrelin acts to affect impulsivity.

“Our results showed that restricting ghrelin effects to the ventral tegmental area, the part of the brain that is a crucial component of the reward system, was sufficient to make the rats more impulsive. Importantly, when we blocked ghrelin, the impulsive behavior was greatly reduced,” says Karolina Skibicka. Even a short period of fasting, a more natural way of increasing the release of ghrelin, increased impulsive behavior.

Impulsivity is a distinctive feature of many neuropsychiatric disorders and behavior disorders such as ADHD, obsessive compulsive disorder (OCD), autism spectrum disorder (ASD), drug abuse and eating disorders.

The study also showed that increased levels of ghrelin even caused long-term genetic changes in the brain circuits that are linked to impulsivity and decision making. A ghrelin injection into the brain that resulted in impulsive behavior in rats, caused the same type of changes in dopamine related genes and enzymes as can be seen in ADHD and OCD.

“Our results indicate that the ghrelin receptors in the brain can be a possible target for future treatment of psychiatric disorders that are characterized by problems with impulsivity and even eating disorders,” says Karolina Skibicka.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160509085807.htm Original web page at Science Daily

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* Stem cells from diabetic patients coaxed to become insulin-secreting cells

If damaged cells are replaceable, type 1 diabetics wouldn’t need insulin shots.

Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St. Louis and Harvard University have produced insulin-secreting cells from stem cells derived from patients with type 1 diabetes.

People with this form of diabetes can’t make their own insulin and require regular insulin injections to control their blood sugar. The new discovery suggests a personalized treatment approach to diabetes may be on the horizon — one that relies on the patients’ own stem cells to manufacture new cells that make insulin.

The researchers showed that the new cells could produce insulin when they encountered sugar. The scientists tested the cells in culture and in mice, and in both cases found that the cells secreted insulin in response to glucose.

“In theory, if we could replace the damaged cells in these individuals with new pancreatic beta cells — whose primary function is to store and release insulin to control blood glucose — patients with type 1 diabetes wouldn’t need insulin shots anymore,” said first author Jeffrey R. Millman, PhD, an assistant professor of medicine and of biomedical engineering at Washington University School of Medicine. “The cells we’ve manufactured sense the presence of glucose and secrete insulin in response. And beta cells do a much better job controlling blood sugar than diabetic patients can.”

Millman, whose laboratory is in the Division of Endocrinology, Metabolism and Lipid Research, began his research while working in the laboratory of Douglas A. Melton, PhD, Howard Hughes Medical Institute investigator and a co-director of Harvard’s Stem Cell Institute. There, Millman had used similar techniques to make beta cells from stem cells derived from people who did not have diabetes. In these new experiments, the beta cells came from tissue taken from the skin of diabetes patients.

“There had been questions about whether we could make these cells from people with type 1 diabetes,” Millman explained. “Some scientists thought that because the tissue would be coming from diabetes patients, there might be defects to prevent us from helping the stem cells differentiate into beta cells. It turns out that’s not the case.”

Millman said more research is needed to make sure that the beta cells made from patient-derived stem cells don’t cause tumors to develop — a problem that has surfaced in some stem cell research — but there has been no evidence of tumors in the mouse studies, even up to a year after the cells were implanted.

He said the stem cell-derived beta cells could be ready for human research in three to five years. At that time, Millman expects the cells would be implanted under the skin of diabetes patients in a minimally invasive surgical procedure that would allow the beta cells access to a patient’s blood supply.

“What we’re envisioning is an outpatient procedure in which some sort of device filled with the cells would be placed just beneath the skin,” he said.

The idea of replacing beta cells isn’t new. More than two decades ago, Washington University researchers Paul E. Lacy, MD, PhD, now deceased, and David W. Scharp, MD, began transplanting such cells into patients with type 1 diabetes. Still today, patients in several clinical trials have been given beta cell transplants with some success. However, those cells come from pancreas tissue provided by organ donors. As with all types of organ donation, the need for islet beta cells for people with type 1 diabetes greatly exceeds their availability.

Millman said that the new technique also could be used in other ways. Since these experiments have proven it’s possible to make beta cells from the tissue of patients with type 1 diabetes, it’s likely the technique also would work in patients with other forms of the disease — including type 2 diabetes, neonatal diabetes and Wolfram syndrome. Then it would be possible to test the effects of diabetes drugs on the beta cells of patients with various forms of the disease.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160510132809.htm  Original web page at Science Daily

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* Rare human disease found in dogs

A rare, severe form of pulmonary hypertension, which up until now, has only been classified as a human lung disease, has also been discovered in dogs according to a Michigan State University study.

“Our research is the first to document the existence of pulmonary veno-occlusive disease, or PVOD, in dogs,” said Kurt Williams, the lead author of the study and an expert in respiratory pathology in MSU’s College of Veterinary Medicine. “PVOD is considered one of the most severe forms of pulmonary hypertension.” The study is published in the journal Veterinary Pathology.

The number of pulmonary hypertension, or PH, cases reported in the United States is low, affecting 15 to 50 people per million each year. PVOD is diagnosed in only about 10 percent of PH cases where no other cause of the disease has been determined. Unfortunately, there are very few effective treatment options for PVOD and a lung transplant often becomes the best choice.

“PVOD might be more common in dogs than in people, but this has yet to be determined and needs to be looked at further,” Williams said.

Pulmonary hypertension develops because of abnormal blood vessels in the lungs, which makes it harder for the heart to push blood through and provide oxygen to the rest of the body. In cases of PVOD, the small veins in the lungs become blocked, increasing pressure in these blood vessels, and ultimately causing heart failure.

“The same process happens in canines,” Williams said. “These dogs also come in with similar symptoms as humans, yet because subtle changes in health may not be recognized as quickly in dogs, death can occur quickly once the animal is seen by a veterinarian.”

Symptoms include cough, increased rate of breathing, respiratory distress, loss of appetite and chronic fatigue. Fatal progression of the disease in humans can last up to two years.

“PVOD is a poorly understood disease not just because it’s so rare, but also because there’ve been no other animals known to have the disease,” Williams said. “Our finding changes things.”

Williams said that the discovery could be important for human medicine because the canine disease may serve as a model for human PVOD.

“It’s cases like this that help to remind us how important veterinary medicine is to medicine in general,” he said. “Our colleagues in the human medical community are becoming much more aware of the many diseases shared by our respective patients and how together we can learn from each other.”

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160512160654.htm  Original web page at Science Daily

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Long-term survival achieved in metastatic melanoma with personalized vaccine

Robert O. Dillman, MD, formerly Vice President Oncology, Caladrius Biosciences, Inc. and currently Chief Medical Officer, NeoStem Oncology (Irvine, CA) and Executive Medical and Scientific Director, Hoag Cancer Institute (Newport Beach, CA) discusses the typically poor prognosis for patients with melanoma of the eye or skin that spreads to the liver, and reports on the potential to achieve long-term survival without disease progression in a subset of patients using the eltrapuldencel-T vaccine. One patient had no disease progression for more than 4.5 years, while the other patient survived and remained disease-free for more than 12 years.

The article “Long-term Progression-free and Overall Survival in Two Melanoma Patients Treated with Patient-Specific Therapeutic Vaccine Eltrapuldencel-T After Resection of a Solitary Liver Metastasis” provides a detailed discussion of the composition and use of the vaccine and its effectiveness in these patients.

“These exciting results illustrate the potential for melanoma patient-specific therapeutic vaccines to enhance long-term survival and add to the progress being made on the immmunotherapy of melanoma,” says Co-Editor-in-Chief Donald J. Buchsbaum, PhD, Department of Radiation Oncology, Division of Radiation Biology, University of Alabama at Birmingham.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/05/160510165122.htm Original web page at Science Daily

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Human-embryo editing now covered by stem-cell guidelines

The international society that represents stem-cell scientists has updated its research guidelines in the wake of dramatic progress in several fields — in particular in research that involves the manipulation of human embryos. The authors hope that the updated guidelines will allay various ethical concerns, and avoid the need for strict government regulations that could impede the progress of science.

“Self-regulation is the best form of regulation,” says Charles Murry, a member of the committee that updated the guidelines, and a bioengineer at the University of Washington in Seattle. “The biomedical community is best poised to strike the balance between rapid progress and safe, ethical research practice.”

The International Society for Stem Cell Research (ISSCR), which was founded in 2002, has previously released guidelines in 2006 and 2008 on embryonic-stem-cell research and on clinical translation of stem-cell research. The latest guidelines have broader scope, and cover all research on human embryos — including gene-editing of embryos, which has in the past year advanced significantly and generated much controversy.

The revised guidelines recommend that all research involving the manipulation of human embryos now undergo a similar review as experiments that use embryos to create stem-cell lines, which has been one of the most divisive research procedures of recent decades. They suggest that such research be added to the remit of existing embryonic stem cell research oversight (ESCRO) committees.

Scientists previously balked at the introduction of ESCRO committees, and there is likely to be resistance to the idea of adding bureaucratic review to other research areas. “No scientist or physician jumps for joy when new regulations are put in place,” says Murry. But he says that the updates are necessary to avoid “a wild-west environment where sensitive research is done without proper regard for community standards”.

At the same time, the new guidelines attempt to clear the way for more research using induced pluripotent stem (iPS) cells, which, like embryonic stem cells, are able to turn into all cell types in the human body but are not taken from embryos. The authors recommend explicitly excluding the generation of iPS cells from regulations on embryonic stem cell research and relying instead on the existing oversight for donor cell recruitment. Some institutions have been confused about how to classify iPS cells, says George Daley, a stem-cell scientist at the Boston Children’s Hospital in Massachusetts and one of the authors of the new guidelines.

Also included in the guidelines is a call for continued observance of a moratorium on growing human embryos in vitro beyond 14 days — a somewhat arbitrary limit that has become the global standard. Two papers published on 4 May reported experiments that showed that it would soon be possible to breach the limit, sparking debate about whether the rule should be reconsidered.

“The ISSCR deserves credit for bringing up and discussing these important issues,” says stem-cell biologist Ali Brivanlou of the Rockefeller University in New York City, who is a lead author on one of the embryo papers. But he adds that further discussion of the issues is needed.  “We need to get together the positives and negatives of moving forward,” he says.

The authors also take the opportunity to reinforce a warning that the ISSCR has long made — that researchers shouldn’t overstate the clinical implications of stem-cell experiments. Hype surrounding such experiments has enabled a worldwide market for unproven, and often ineffective or dangerous, stem-cell therapies, which has been difficult to regulate. “We take a swipe at hyperbole in scientific communication, essentially asking researchers to ‘take it down a notch’ when they speak about the implications of their work,” says Murry.

Nature doi:10.1038/nature.2016.19909

http://www.nature.com/news/index.html  Nature

http://www.nature.com/news/human-embryo-editing-now-covered-by-stem-cell-guidelines-1.19909  Original web page at Nature

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* Tiny coils improve quality of life for patients with severe emphysema

The minimally invasive implantation of tiny coils into the lungs improves exercise ability, lung function and quality of life for patients with severe emphysema, according to a large international trial presented by researchers at the University of Pittsburgh School of Medicine. The findings were published in the Journal of the American Medical Association and presented today at the American Thoracic Society International Meeting in San Francisco.

“Some patients with advanced emphysema have few treatment options, and this trial significantly furthers our understanding of the potential role of minimally invasive lung volume reduction therapy as an option to improve symptoms,” said lead author Frank Sciurba, M.D., director of the UPMC Pulmonary Function and Exercise Physiology Laboratory, and professor, Division of Pulmonology, Allergy and Critical Care Medicine at Pitt.

Patients with emphysema, a form of chronic obstructive pulmonary disease (COPD), experience an over-inflation of the lungs that limits their ability to breathe deeply, resulting from progressive destruction of the air sacs of their lungs and collapse of the airways. The coils are intended to improve the elastic properties of the lungs to prevent collapse of the airways, allowing patients to exhale more completely, Dr. Sciurba explained.

The study included 315 patients recruited at 26 sites in the U.S. and Europe between December 2012 and November 2015. With over 75 percent of study participants experiencing severe symptoms yet having a pattern of emphysema not allowing them to be candidates for surgery or experimental valve treatment, those patients had few therapeutic options short of lung transplantation.

Participants were randomly assigned to either standard care, which included optimal inhaler medications and pulmonary rehabilitation, or to receive standard care plus bilateral coil insertion placed in the most severely affected lobe of each lung.

The researchers measured how far participants could walk in six minutes, both at baseline and after 12 months of treatment. Patients who received coils showed a modest improvement in walking distance at 12 months, while the usual care group declined in function over the same time period.

After one-year follow-up, the coil group overall was able to walk 15 meters farther than the usual care group in the allotted six minutes. Forty percent of the coil group was able to walk an additional 25 meters more, while only 27 percent of the non-coil group achieved those walking gains.

Forced expiration of air, the most common measure of lung function in emphysema patients, also improved in those receiving coils more so than in those who didn’t receive them.

Patients receiving coils reported dramatic improvement in their quality of life, which is measured by the emphysema-specific St. George’s Respiratory Questionnaire, with 32 percent more patients in the coil group achieving a meaningful level of self-reported improvement over those in the non-coil group.

The benefits of the coils did come at a cost–initially, patients had a significantly higher rate of major complications such as pneumonia and pneumothorax than those in usual treatment group. However, the increased risk of serious adverse events appeared to be short lived. By nine months, there was no difference between the two groups. There also was no difference in the death rate measured at 12 months.

The investigators learned over the course of the study that some of the events initially thought to be pneumonia may in fact be changes in the X-ray due to tension from the coils that may in the long run result in a better patient improvement.

Additional findings by the investigators identified patients who may achieve the greatest benefit from coils. Patients with the greatest degree of lung over-inflation had the greatest improvements in walk distance and symptoms compared to the least over-inflated patients. Also, patients with additional medical issues beyond COPD appeared to improve less.

“Overall, the coils provided a modest improvement in exercise ability and lung function, and a very clinically important improvement in quality of life, but with a higher likelihood of major complications,” Dr. Sciurba said. “This provides an evidence-based choice for symptomatic patients with few options.”

The U.S. Food and Drug Administration (FDA) will now determine whether the coils are ready for widespread use, he added.

UPMC’s Division of Pulmonology, Allergy and Critical Care Medicine has a long history of pioneering treatments for lung disease, beginning with innovations in lung volume reduction surgery in the mid-1990s and continuing with active involvement in clinical trials aimed at providing a less invasive treatment approach. UPMC also is home to a leading lung transplant program.

“This trial represents an extension of a 20-year legacy of UPMC leadership in surgical and bronchoscopic lung volume reduction approaches,” said division chief Rama Mallampalli, M.D.

https://www.sciencedaily.com/  Science Daily

https://www.sciencedaily.com/releases/2016/05/160515183719.htm  Original web page at Science Daily