Category: Health

{Using a novel form of gene therapy, scientists from Harvard Medical School and the Massachusetts General Hospital have managed to restore partial hearing and balance in mice born with a genetic condition that affects both.}

The new model overcomes a long-standing barrier to accessing hair cells, the delicate sensors in the inner ear that capture sound and head movement and convert them to neural signals for hearing and balance. These cells have been notoriously difficult to treat with previous gene-delivery techniques.

The team’s findings, published in the February issue of Molecular Therapy, show that the treatment leads to notable gains in hearing and allows mice that would normally be completely deaf to hear the equivalent of a loud conversation. The approach also improved the animals’ sense of balance.

An accompanying commentary to the study appears in the same issue.

The investigators caution the approach is years away from use in humans, but gene therapy carries the promise of restoring hearing in people with several forms of both genetic and acquired deafness. Some 30 million Americans suffer from hearing loss, and every year about one in 1,000 babies are born with hearing impairment, according to the Centers for Disease Control and Prevention.

On their quest to restore hearing through gene therapy, scientists have long sought ways to improve gene delivery into hair cells. Previous approaches were only marginally effective as they reached one set of hair cells in the inner ear, but another subset — equally critical for hearing — remained largely impenetrable.

“To treat most forms of hearing loss, we need to find a delivery mechanism that works for all types of hair cells,” said neurobiologist David Corey, co-senior investigator on the study and the Bertarelli Professor of Translational Medical Science at HMS.

To achieve that, the researchers used the common adeno-associated virus (AAV). The virus has been already used as a gene-delivery vehicle for retinal disorders but thus far has proven far less efficient in penetrating hair cells.

To super-charge AAV as a gene carrier into the inner ear, the team used a form of the virus wrapped in protective bubbles called exosomes, an approach recently developed by study co-investigators Casey Maguire, HMS assistant professor of neurology at the Mass General, and Xandra Breakefield, HMS professor of neurology at Mass General.

Maguire and colleagues grew regular AAV virus inside cells. Those cells naturally bud off exosomes — tiny bubbles made of cell membrane — that carry the virus inside them. The membrane wrapping around the virus is coated with proteins that bind to cell receptors. This, Maguire said, may be the reason why the bubble-wrapped form of AAV, or exo-AAV, binds more easily to the surfaces of hair cells and penetrates them more efficiently.

“Unlike current approaches in the field, we didn’t change or directly modify the virus. Instead, we gave it a vehicle to travel in, making it better capable of navigating the terrain inside the inner ear and accessing previously resistant cells,” said Maguire, who is also co-senior author on the study.

In lab dish experiments, exo-AAV successfully penetrated 50-60 percent of hair cells, the researchers observed. By contrast, AAV alone reached a mere 20 percent of hair cells.

To test the approach in living animals, the researchers worked with mice born without a gene critical for hair cell function. Such animals normally cannot hear even the loudest sounds and exhibit poor balance.

Researchers Bence György and Cyrille Sage, first authors on the study, injected exo-AAV preloaded with the missing gene into the inner ears of mouse pups, shortly after birth.

Post-treatment tests revealed that the gene entered between 30 and 70 percent of hair cells, reaching both inner and outer hair cells.

A month after treatment, nine of 12 mice had some level of hearing restored and could be startled by a loud clap, a standard behavioral test for hearing. Four could hear sounds of 70 to 80 decibel intensity, the rough equivalent of conversation in a loud restaurant.

Because hair cells are also critical for the sense of balance, mice with damaged or missing hair cells show balance abnormalities. Treated mice had notably improved balance, compared with their untreated counterparts, showing far less head tossing or running in circles, both markers of instability or disorientation.

The team now plans to improve their gene-delivery technique in an attempt to reach an even greater proportion of hair cells. The scientists will test the approach in other forms of deafness, including conditions that cause both deafness and blindness.

{There is a general belief that to build your muscles, you ought to lift heavy weights. However, a 2010 study found that building muscle depends on achieving muscle fatigue and not on pumping heavy weights as previously believed.}

The study conducted at McMaster University has shown that a similar degree of muscle building can be achieved by using lighter weights. The secret is to pump iron until you reach muscle fatigue.

“Rather than grunting and straining to lift heavy weights, you can grab something much lighter but you have to lift it until you can’t lift it anymore,” says Stuart Phillips, associate professor of kinesiology at McMaster University. “We’re convinced that growing muscle means stimulating your muscle to make new muscle proteins, a process in the body that over time accumulates into bigger muscles.”

Study shows 400,000 children with developmental disorders born each year globally.

The largest ever genetic study of children with previously undiagnosed rare developmental disorders has discovered 14 new developmental disorders. Published today in Nature, the research led by scientists at the Wellcome Trust Sanger Institute also provided diagnoses of rare conditions for over a thousand children and their families.

These diagnoses allow families with the same genetic conditions to connect and access support, and help inform better clinical management. The study also accelerates research into disease mechanisms and possible therapies.

Each year, thousands of babies are born who do not develop normally because of errors in their genetic makeup. This can lead to conditions such as intellectual disability, epilepsy, autism or heart defects. There are over 1,000 recognised genetic causes, however many individual developmental disorders are so rare that the genetic causes are not known. The Deciphering Developmental Disorders (DDD) study aims to find diagnoses for children with as yet unknown developmental diseases, and demonstrate that new genomic technologies can provide improved diagnostic tests.

Working with 200 NHS clinical geneticists, the researchers screened all 20,000 human genes from more than 4,000 families, from across the UK and Republic of Ireland, with at least one child affected by a developmental disorder. The DDD team focused on spontaneous new mutations that arise as DNA is passed on from parents to children. The children’s conditions were also clinically assessed and the team combined the results to match up children with similar disorders to provide diagnoses.

The study team was able to diagnose children who had new mutations in genes already linked to developmental disorders — approximately one quarter of the patients in the study. In addition, they identified 14 new developmental disorders, all caused by spontaneous mutations not found in either parent.

Dr Jeremy McRae, first author from the Wellcome Trust Sanger Institute, said: “Each of these disorders is incredibly rare, so the large number of patients in this study was crucial to diagnosis. An individual doctor may see only one case, but by collaborating with hundreds of NHS staff and researchers we were able to link children from clinics across the British Isles. This allowed the team to match up children with similar disorders within the project and provide diagnoses for them.”

Professor David FitzPatrick, a supervising author from the MRC Human Genetics Unit at the University of Edinburgh, said: “Families search for a genetic diagnosis for their children, as this helps them understand the cause of their child’s disorder. This can help doctors better manage the child’s condition, and gives clues for further research into future therapeutics. In addition to this, a diagnosis can let parents know what the future holds for their child and the risk of any subsequent pregnancies being affected with the same disorder, which can be an enormous help if they want a larger family.”

Overall, the researchers estimated that for 42 per cent of the children in the study, a new mutation in a gene important for healthy development is likely to be the underlying cause of their condition. The DDD study also estimated that, on average, 1 in 300 children born in the UK have a rare developmental disorder caused by a new mutation. This adds up to 2,000 children a year in the UK.

They also demonstrated that older parents have a higher risk of having a child with a developmental disorder caused by a new mutation. The chances rose from 1 in 450 for 20-year old parents having a child with a rare developmental disorder to 1 in 210 for 45 year-old parents.

From this, the researchers calculated that nearly 400,000 of the 140 million annual births across the world will have a developmental disorder caused by a spontaneous new mutation that is not carried by either parent.

Dr Matt Hurles, who led the study from the Sanger Institute, said: “This study has the largest cohort of such families in the world, and harnesses the power of the NHS, with 200 clinical geneticists and 4,000 patients. The diagnoses we found were only possible because of the great collaborative effort. Finding a diagnosis can be a huge relief for parents and enables them to link up with other families with the same disorder. It lets them access support, plug into social networks and participate in research projects for that specific disorder.”

{If your New Year’s resolution was to exercise more in 2017, chances are you’ve already given up or you’re on the verge of doing so. To reach your goal, you may want to consider joining a gym, based on the results of a new study from a team of Iowa State University researchers.}

Duck-chul (DC) Lee, an assistant professor of kinesiology and corresponding author of the paper, says the study found people who belonged to a health club not only exercised more — for both aerobic activity and strength training — they also had better cardiovascular health outcomes. Those health benefits were even greater for people who had a gym membership for more than a year, Lee said. The research is published in the journal PLOS ONE.

“It’s not surprising that people with a gym membership work out more, but the difference in our results is pretty dramatic,” Lee said. “Gym members were 14 times more aerobically active than non-members and 10 times more likely to meet muscle-strengthening guidelines, regardless of their age and weight.” The results were similar in both men and women.

It’s recommended that adults get 150 minutes of moderate or 75 minutes of vigorous aerobic activity each week, such as brisk walking or running. The Physical Activity Guidelines also suggest two days of weight lifting or other muscle-strengthening activities. Despite strong evidence of the health benefits, only half of Americans are getting enough aerobic activity and about 20 percent meet the guidelines for strength training.

Iowa State researchers found 75 percent of study participants with gym memberships, compared to 18 percent of non-members, met the guidelines for both types of activity. In fact, the majority of those who went to a health club exceeded standards and spent 300 minutes or more running, biking or doing some type of cardio workout each week. That adds up to nearly six hours of additional activity, compared to non-members.

Gym members overall had a more active lifestyle. Researchers say members were just as active outside the gym and in their daily lives, which combined contributed to better health outcomes. Here are a few of the results for members:

• Lower odds of being obese — weight loss is a main reason for joining a gym • Smaller waist circumference — about 1.5 inches less for men and a similar trend for women • Lower resting heart rate — about five beats lower than non-members • Higher cardiorespiratory fitness — this measures heart strength, lung function, blood circulation and muscle mass

Elizabeth Schroeder, lead author and a former Iowa State graduate student, says while most people join a gym to lose weight, the research shows the many benefits of exercise.

“Cardiovascular disease is the leading cause of death for individuals in the U.S. As our paper shows, a health club membership is associated with more favorable cardiovascular health,” Schroeder said. “I hope the results help people be more active, potentially at a health club where they can easily perform resistance exercise, and see that exercise may help prevent cardiovascular disease.”

This is also one of the first studies to measure weight lifting and resistance exercise. Lee says this type of activity is beneficial because it builds muscle mass, which burns more energy and lowers the risk of obesity and the risk of sarcopenia for older adults.

Researchers did not ask participants if they spend time at the gym running on a treadmill, riding a bike, attending a group fitness class or other activity. However, Warren Franke, a co-author and professor of kinesiology, says health clubs offer a variety of options and benefits for people who are new to exercise. Franke is director of Iowa State’s Exercise Clinic.

“By joining a quality fitness facility, a new exerciser will be around like-minded people and have access to professionals who can help them be successful,” Franke said. “Access to quality exercise equipment, social support and even the financial commitment may help spur someone to continue exercising. Not all facilities are the same, so it’s important to find the ‘right’ fit.”

Incentivizing workouts

Most people spend much of their day sitting at a desk, and do little heavy lifting to create resistance against their muscles. Increasing activity levels lowers the risk for diseases such as Type 2 diabetes and cardiovascular disease, Lee said. However, only 18 percent of Americans have a gym membership. Based on the research results, incentives to boost membership could be beneficial, Lee said.

Several companies have on-site workout facilities for employees or provide some form of reward for going to the gym. Greg Welk, a co-author and professor of kinesiology, says efforts to increase these opportunities not only improves employee health, but also reduce sick days and lower insurance costs. As a coordinator of the ISU’s Wellness Works, Welk provides companies with the tools and support to implement effective wellness programming.

“Access to fitness facilities can provide employees with an incentive to take responsibility and adopt regular habits of physical activity,” Welk said. “A fitness center can promote improved fitness, but employees may also need support for eating habits, managing stress and other health needs.”

Researchers say it’s important to note that some data for the study were collected while people were at the gym, which would exclude people who have a membership, but are not using it. It is also a cross-sectional study, so researchers cannot directly state a cause and effect.

{How does heightened attention improve our mental capacity? This is the question tackled by new research published today in the journal Cell Reports, which reveals a chemical signal released across the brain in response to attention demanding or arousing situations.}

The new discoveries indicate how current drugs used in the treatment of Alzheimer’s, designed to boost this chemical signal, counter the symptoms of dementia. The results could also lead to new ways of enhancing cognitive function to counteract the effects of diseases such as Alzheimer’s and schizophrenia, as well as enhancing memory in healthy people.

The team of medical researchers at the Universities of Bristol and Maynooth in collaboration with pharmaceutical company Eli Lilly & Company, studied how the release of the chemical ‘acetylcholine’ fluctuates during the day but found that the release is at its highest when the brain is engaged with more challenging mental tasks. The fluctuations are coordinated across the brain indicating a brain-wide signal to increase mental capacity with specific spikes in acetylcholine release occurring at particularly arousing times such as gaining reward.

Professor Jack Mellor, lead researcher from Bristol’s Centre for Synaptic Plasticity, said: “These findings are about how brain state is regulated and updated on a rapid basis to optimise the encoding of memory and cognitive performance. Many current and future drug therapies for a wide range of brain disorders including Alzheimer’s and schizophrenia are designed to target chemical systems such as acetylcholine so understanding when they are active and therefore how they function will be crucial for their future development and clinical use.”

Professor Lowry, who led the team at Maynooth University, added: “This work highlights the importance of cross-disciplinary basic research between universities and industry. Using real-time biosensor technology to improve our understanding of the role of important neurochemicals associated with memory is very exciting and timely, particularly given the increasing multifaceted societal burden caused by memory affecting neurological disorders such as dementia.”

Primary author Dr Leonor Ruivo added: “This collaboration gave us access to a new generation of tools which, in combination with other powerful techniques, will allow researchers to build on our findings and provide a much more detailed map of the action of brain chemicals in health, disease and therapeutic intervention.”

The research team involved the University of Bristol’s Centre for Synaptic Plasticity within the School of Physiology, Pharmacology & Neuroscience and the University of Maynooth department of Chemistry in collaboration with researchers at Lilly. The work was supported by the Wellcome Trust, BBSRC and Lilly.

{Objective sleep outcomes were unchanged in women experiencing hot flashes during the menopausal transition or after menopause.}

A new study indicates that yoga and aerobic exercise interventions did not significantly reduce objectively measured sleep disturbances among midlife women who were experiencing hot flashes.

Secondary analyses of a randomized controlled trial show that neither 12 weeks of yoga nor 12 weeks of aerobic exercise had a statistically significant effect on objective measures of sleep duration or sleep quality recorded by actigraphy. Although the women had no difficulty falling asleep, disturbed sleep was common at baseline and remained after each intervention, with women in all groups waking during the night for an average of more than 50 minutes.

According to the authors, previously published analyses of the same trial had found that the yoga and aerobic exercise interventions were associated with small but statistically significant improvements in subjective, self-reported sleep quality and insomnia severity.

“Our primary findings were that the two study interventions had no significant effects on objective sleep outcomes in midlife women with hot flashes. The main implication of this finding is that other behavior treatments with the potential for effectively improving sleep in this population should be examined,” said lead author Diana Taibi Buchanan, associate professor of Bio-Behavioral Nursing and Health Informatics at the University of Washington in Seattle.

Study results are published in the Jan. 15 issue of the Journal of Clinical Sleep Medicine.

The authors analyzed data from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) network. The study involved 186 late transition and postmenopausal women with hot flashes who were between 40 and 62 years of age. Study subjects had an average of 7.3 to 8 hot flashes per day. Participants were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity.

Sleep measures were evaluated using wrist actigraphy, and bedtimes and rise times were determined primarily from the participants’ sleep diaries. Mean sleep duration at baseline and after each intervention was less than the 7 or more hours of nightly sleep that is recommended by the American Academy of Sleep Medicine for optimal health in adults.

According to the authors, future research should explore other approaches for improving sleep quality in midlife women, such as cognitive behavioral therapy for insomnia.

{Today, a stroke usually leads to permanent disability — but in the future, the stroke-injured brain could be reparable by replacing dead cells with new, healthy neurons, using transplantation. Researchers at Lund University in Sweden have taken a step in that direction by showing that some neurons transplanted into the brains of stroke-injured rats were incorporated and responded correctly when the rat’s muzzle and paws were touched.}

The study, published in the journal Brain, used human skin cells. These cells were re-programmed to the stem cell stage and then matured into the type of neurons normally found in the cerebral cortex.

A couple of years ago, the research team at the Stem Cell Centre in Lund had already proven that transplanting this type of cells to the cerebral cortex enabled stroke-injured rats to move better. At the time, however, it was unclear whether the host brain really formed functioning connections with the transplanted nerve cells. Now the new study has proven that this is indeed the case.

The research team used several advanced methods in the study — electron microscopy, virus-based tracing techniques, registration of activity in the transplanted cells and optogenetics. The results show that various parts of the host brain form normal, functioning connections with the transplanted neurons and that the latter change their activity when the animal’s muzzle and paws are touched.

“This is the first time anyone has been able to show such a result. That some of the new nerve cells receive signals from the host brain in a normal way indicates that they have been incorporated into the stroke-injured rat’s brain. In it, they have been able to replace some of the dead nerve cells,” says the professor at the Stem Cell Centre, Zaal Kokaia.

Now, a stroke-injured laboratory animal is not the same as a stroke patient. But professor and consultant physician Olle Lindvall, who is also part of the research team, still sees the team’s study as an important first step. It constitutes what is known as proof of concept, showing that it is possible to replace dead neurons with new, healthy cells through transplantation after a stroke.

“This is basic research, and it is not possible to say when we will be ready to start experiments on patients. But the objective is clear: to develop a treatment method which can repair the stroke-injured brain. Currently, there is no effective treatment which can restore function in a stroke patient once the first hours following a stroke have passed,” says Zaal Kokaia.

{Zika virus prevents human neural cells to grow, multiply and specialize.}

Zika virus (ZIKV) interferes with the cellular machinery controlling cell division and alters the expression of hundreds of genes responsible for guiding the formation and development of brain cells, according to findings released on January 23 by Scientific Reports.

The association between Zika virus (ZIKV) infection and microcephaly has been previously established. Nevertheless, the cellular changes caused by the virus and leading to microcephaly are largely unknown. “Elucidating the foundations of Zika virus infection is crucial in order to develop tools against it,” says Stevens Rehen, the principal investigator of the study and a researcher working at the D’ Or Institute for Research and Education (IDOR) and at the Institute of Biomedical Sciences at Federal University of Rio de Janeiro (UFRJ) in Brazil.

In a previous study published by the group in Science magazine, researchers observed that the pool of human neural stem cells infected by the Brazilian strain of Zika virus was rapidly and completely depleted, if compared to non-infected cells. This finding led the group to further investigate how Zika virus disrupts the interactome map (or molecular fingerprinting) of infected cells — which is the entire set of cellular and molecular interactions in a given cell group. The analysis of the interactome of Zika-infected cells may reveal the cellular targets and pathways with which the virus interacts or which it modulates, offering valuable opportunities for drug design.

To this end, human neural cells were infected by a strain of ZIKV obtained from a Brazilian patient. These cells were then made into neurospheres, which are organized 3D aggregates of neural cells resembling fetal brain tissue that recapitulate many of the normal early and crucial processes that the brain undergoes through development and thus are a great model for studying the human brain. Next, the group identified the molecular fingerprinting of infected and non-infected cells by checking the expression level and status of innumerous genes and proteins.

The analysis revealed that more than 500 proteins in infected neurospheres had their expression level or status (upregulated vs downregulated) altered, if compared to non-infected neurospheres. A number of these altered proteins are normally involved with tasks such as fixing DNA damage or assuring chromosomal stability. Also, proteins that are normally required for cell growth were silent in infected neurospheres, which may explain why Zika-infected cells die much sooner than their non-infected counterparts. Interestingly, genes driving cell specialization were also silent in infected neurospheres, precluding that specialized brain cells were generated. On the other hand, proteins associated with viral replication were over-abundant, most likely the result of a strategy adopted by the virus to promote its own replication in the host cell. A complete list of all human proteins that have been found altered in Zika-infected neurospheres is available in the study entitled “Zika virus disrupts molecular fingerprinting of human neurospheres,” published in Scientific Reports this week.

According to Patricia Garcez, Assistant Professor at the Federal University of Rio de Janeiro and the first author of the study: “these findings provide insights into the molecular mechanisms of ZIKV infection over the course of brain development and may explain some of the consequences seen in the brain of newborns with microcephaly.”

{Has enough been said about being sedentary and a lack of exercise? So many researches have found the dangers of being sedentary and not exercising, and a recent research has gone on to reveal how they can make one age faster.}

Researchers at University of California San Diego School of Medicine report that elderly women who sit for more than 10 hours a day with low physical activity have cells that are biologically older by eight years compared to women who are less sedentary.

Nearly 1,500 women, ages 64 to 95, participated in the study.

According to Aladdin Shadyab, PhD, lead author of the study with the Department of Family Medicine and Public Health at UC San Diego School of Medicine: “Our study found cells age faster with a sedentary lifestyle. Chronological age doesn’t always match biological age.”

“We found that women who sat longer did not have shorter telomere length if they exercised for at least 30 minutes a day, the national recommended guideline,” said Shadyab. “Discussions about the benefits of exercise should start when we are young, and physical activity should continue to be part of our daily lives as we get older, even at 80 years old.”

The importance of taking walks, engaging in regular exercises and avoiding being sedentary cannot be overemphasized.