Clinical Trial

People With Autism Have More Symmetrical Brains. Here’s What That Could Mean

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In spite of how they appear, the left and right hemispheres of the human brain tend to be far from perfect reflections of each other. Some neurological disorders can affect that imbalance, causing the two halves to appear strikingly alike.

So far, studies on whether autism is among those conditions have been less than convincing. To get a more definitive answer, researchers analysed thousands of brains and showed there is slightly more symmetry for those on the spectrum.

But what does that really mean?

To get this answer, scientists from the Enhancing Neuro-Imaging Genetics through Meta-Analysis consortium collected decades of brain scans from more than 1,700 individuals diagnosed with autism spectrum disorder (ASD) and more than 1,800 with no diagnosis.

The consortium were hardly strangers to analysing huge banks of data, having only recently conducted a similar study on ASD brain anatomy involving more than 3,000 subjects.

The condition covers a spectrum of characteristics that can make life a little more challenging for some, affecting their ability to socialise, communicate, and process stimuli.

With such variation in behaviours, sensations, and impact, tracing the traits making up ASD down to simple neurological differences is no easy task.

Doing so could help make the disorder easier to diagnose and lead to novel therapies, opening the way to providing better methods of assistance for those who need it.

So researchers have been busy looking for clues on all levels of anatomy, from the genes to the gross architecture of our squishy bits.

There have been plenty of investigations into the overall structures of autism-related brains, discovering subtle differences such as the thickness of the cerebral cortex and how key areas link together.

Comparing the ways our brain’s mirrored hemispheres reflect each other is a fair way to understand how they develop and communicate.

After all, for most of us, it’s differences both between and within the two halves that governs everything from movement to cognitive processes.

Unfortunately, there’s still so much we don’t know about this contrast between the hemispheres, or ‘lateralisation’. So when it comes to learning how lateralisation might be linked with more profound neurological differences, we’re still in the dark ages.

There are studies that have found people with ASD have unusually symmetrical brains. There are also studies that found no such thing.

They also tend to be more left handed, and seem less symmetrical in other areas of the brain.

If you’re confused about what to make of the mess of conflicting studies, you’re not the only one.

“Previous studies have suggested that people with autism spectrum disorder are less likely to have the typical asymmetries for language dominance or hand preference,” says geneticist Merel Postema from the Max Planck Institute for Psycholinguistics in the Netherlands.

“However, it has not been clear whether asymmetry of the brain’s anatomy is affected in autism, because different studies have reported different findings.”

Comparing the thickness of the cortex forming key parts of the brain’s outer layer, the researchers found there was comparably less variability across the hemispheres in brains from people with ASD.

These differences didn’t vary much depending on sex, medication, or IQ, making it more likely that there was something about autistic brains that accounted for this increased symmetry.

In spite of the significance of the results, it’s not enough of a difference to base a diagnosis on.

“The very small average differences in brain asymmetry between affected people and controls mean that changes of brain asymmetry will not be useful in terms of clinical prediction”, says the study’s leader, Clyde Francks from the Max Planck Institute for Psycholinguistics.

“But the findings might inform our understanding of the neurobiology of autism spectrum disorder”.

Some of the differences, for example, appeared in areas containing networks that work harder while we’re resting. Just how this might account for some of autism’s traits – if at all – is a task for future studies.

No doubt, there’ll be more research on this in the future. Having more information on how our brain works as a whole not only helps us better understand how ASD arises, but how behaviours and functions common to all of us might develop.

This research was published in Nature Communications.

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ICMR and LSHTM join hands to train healthcare professionals on use of diagnostics in prevention & control of AMR

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The London School of Hygiene and Tropical Medicine (LSHTM) and Indian Council of Medical Research (ICMR) have joined hands to train healthcare professionals about the use of diagnostics in the prevention and control of antimicrobial resistance (AMR).

Health professionals, students or anyone who is interested to learn about the use of diagnostics in the prevention and control of antimicrobial resistance (AMR) can enroll on a first come first served basis.

This is a six week online training course developed by LSHTM.

Training will cover Clinical Syndromes, Healthcare Associated Infections (HAIs), Enteric Infections and Drug Resistant Infections in TB and Role of Diagnostics in AMR.

It will also cover basic concepts of microbes, colonization and infection as diagnostics play a major role to respond to the increased threats being posed by overuse of antibiotics.

It will focus on four bacterial pathogens that cause enteric or food- borne infections in humans and animals and the need to use diagnostics for the prevention and control of AMR.

This will includes Enteric infections, Salmonella spp., Shigella spp. and Escherichia coli.

It will also discuss the role of diagnostics in the detection and surveillance of drug resistance for Mycobacterium tuberculosis and Neisseria gonorrhoeae, two pathogens of public health importance that are rapidly becoming untreatable.

The course will give insights about the global response to AMR, various initiatives put forth by stake holders and the role healthcare professionals can play to control AMR.

Three common clinical syndromes – respiratory infections, urinary tract infections and sepsis will be examined for which the clinical presentation is non- specific and antibiotics are often prescribed presumptively.

It will talk about bacterias that cause healthcare associated infections (HAIs) which will includes Methicillin- resistant Staphylococcus aureus (MRSA), Carbapenemase producing organisms (CPO), Clostridioides di cile (C diff) and Vancomycin-resistant enterococci (VRE)

Healthcare professionals will have a greater awareness of AMR and how it is caused during the online training programme through articles, mini-lectures and interviews with experts in the field to highlight some of the key issues and thinking around the role of diagnostics in response to AMR.

Besides, the training will also include a number of case studies, educational videos, animations and also assess learning through quizzes. This will also involve sharing experiences and views through discussion with fellow learners and the course team besides the reference lists and supplementary reading that can be useful during the study.

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Itchy Skin Conditions And Mental Health Are Linked, And We Need to Talk About It

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Why do we itch? The reasons are many and varied. But what’s becoming ever clearer is many who experience chronic itching due to skin conditions also shoulder a profound psychological burden no scratching can relieve.

While the nature of this link around conditions like eczema and psoriasis has been investigated before, scientists say we’re still only beginning to understand how skin disorders, mental health problems, and quality of life all intersect.

“There are already studies showing evidence of a correlation between itch and mental health problems in general, and in specific skin disorders, but there is a lack of a cross-sectional study across chronic skin diseases,” says dermatologist Florence J. Dalgard from Lund University in Sweden.

To help fill that gap, Dalgard and her team analysed data collected from thousands of dermatology patients with skin issues in 13 European countries, including the UK, France, Germany, Russia, and elsewhere.

In total, over 3,500 patients with varying skin diseases took part in the study, undergoing physical examinations and filling out a questionnaire which asked questions about their socio-economic background and experiences with itching, while also measuring symptoms of depression, anxiety, and suicidal ideation.

More than 1,300 people without skin conditions acted as a control group, self-reporting the same information.

When the research team analysed the responses, they found a number of associations between skin conditions, itching, mood disorders, and quality of life impairments.

In patients with skin conditions who reported itching, the prevalence of depression was 14.1 percent. This lowered to 5.7 percent in patients who didn’t itch.

Controls without skin disorders who reported itching also had around a 6 percent prevalent of depression – while only 3.2 percent in the control group members who didn’t have itching reported depression.

Anxiety bore a similar pattern, showing up in 21.4 percent of the patients with skin conditions and itching, and dropping to 12.3 percent in patients without itching, while approximately 8 percent of the controls reported anxiety.

The prevalence of suicidal ideation was higher in patients with itch (15.7 percent) than in patients without itch (9.1 percent); similarly, it was higher in controls with itch (18.6 percent) than controls without (8.6 percent).

Patients with itch further reported experiencing more negative life events than the patients without itch did (38.2 percent compared to 32.4 percent respectively), and the patients who experienced itching were also likely to experience more economic problems.

While the team acknowledge their data can prove nothing about causation one way or the other (and submit that mental health suffering could potentially induce itch to some degree), they suggest it is much more likely that skin diseases are the cause of itching, which then leads to mental health effects.

“Speculative reasons for this correlation is that itch correlates with skin inflammation and skin inflammation induces serotonin network in the brain leading to depression and anxiety,” the authors write in their paper.

While more research is needed to explore the hypothesis, for now at least, the link between itching and depression looks more firmly established than ever.

And that, the researchers say, should be reflected in how we treat patients with skin conditions – with a multidisciplinary team of physicians to help support these people, and everything they may be dealing with.

At the same time, preventative programs might be able to play a role in helping to ease itching and maybe reducing the development of the serious psychological symptoms that appear to stem from it.

“Our findings demonstrate that the presence of itch in dermatological patients is significantly associated with clinical depression, suicidal ideation and stress,” the researchers conclude.

“The study reveals that itch contributes substantially to the psychological burden of dermatological patients and confirms the multi-dimensional suffering of dermatological patients with itch.”

The findings are reported in Journal of Investigative Dermatology.

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ICMR rolls out ICMR-DHR international fellowship programmes to augment capacity of Indian scientists

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In order to augment capacity of Indian scientists in emerging areas of clinical, medicine and health sciences, Indian Council of Medical Research (ICMR) has rolled out ICMR-DHR (Department of Health Research) international fellowship programme to create a pool of talented health research personnel by facilitating advanced training to the latest advancements in knowledge through interaction with the international scientists.

DHR-ICMR fellowship programme aims to provide advanced training in India and abroad to medical and health research personnel in cutting edge research areas related to medicine and health.

It covers 25 fellowships per year for short term international fellowships for senior Indian biomedical scientists for a duration of two weeks to 3 months. The age limit is below 57 years as on last date of receipt of application.

It also covers 40 long term international fellowships for young Indian biomedical scientists for a duration of of 6 to 12 months. The age limit for the same is below 45 years as on last date of receipt of application. Applications should be submitted online through the website portal of ICMR/DHR at http://www.icmr.nic.in: http://www.dhr.gov.in.

Details of the eligibility, format of application, terms and conditions and guidelines of the programme are available on ICMR and DHR websites. Last date of receipt of applications is December 15, 2019.

Department of Health Research (DHR) under the union health ministry is entrusted with the promotion and co-ordination of basic, applied and clinical research including clinical trials and operational research in areas related to medical, health, biomedical and medical profession and education through development of infrastructure, manpower and skills in cutting edge areas and management of related information thereto.

It is also mandated to promote and provide guidance on research governance issues, including ethical issues in medical and health research.

DHR also covers inter-sectoral coordination and promotion of public-private partnership in medical, bio-medical and health research related areas, advanced training in research areas concerning medicine and health including grant of fellowships for such training in India and abroad, international cooperation in medical and health research including work related to international conferences in related areas in India and abroad.

It also gives technical support for dealing with epidemics and natural calamities.

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FDA Has Fast-Tracked a Long-Awaited Cystic Fibrosis Drug That May Help 90% of Patients

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A new cystic fibrosis therapy dramatically improved patients’ lung function and showed clear signs of targeting the genetic root of the disease, instead of just alleviating symptoms — a breakthrough so long-sought that many doctors and patients are moved to tears when talking about it.

The data, being unveiled Thursday at a national conference in Tennessee and simultaneously published in two leading medical journals, was so persuasive that the Food and Drug Administration last week approved the three-drug combination, called Trikafta — five months ahead of the agency’s deadline.

The drug could benefit 90 percent of patients with the disease, a major advance over previous drugs that worked in a tiny fraction of the people with the disease or had more modest effects.

“I’m overjoyed,” said Francis Collins, the director of the National Institutes of Health, who was part of one of the teams that in 1989 discovered the gene defect that causes cystic fibrosis.

“Thirty years along, with many bumps along the road and so many people waiting and hoping that something like this would happen — and here we are.”

The drug is the product of decades of steady, incremental scientific work that began with research in academic laboratories and was pushed forward and funded by patient advocates through an unusual “venture philanthropy” model now being emulated by other patient groups.

The leap forward was preceded by many steps — Trikafta is the fourth therapy developed by Vertex Pharmaceuticals, a Boston-based company that has built a lucrative franchise around the disease.

Cystic fibrosis affects an estimated 30,000 people in the United States. Thick mucus builds up in the body’s organs, damaging people’s lungs and digestive systems.

Patients wear vibrating vests to break up the mucus and spend hours each day coughing to keep their lungs clear. They assiduously protect themselves from respiratory illnesses that can send them to the hospital.

They often take antibiotics, enzymes and vitamins to stay healthy. The life expectancy of patients has been increasing, and patients born today live on average 44 years.

Doctors who began their careers at a time when there were few adults with cystic fibrosis because patients died in their teens are now cautiously anticipating that the disease will be transformed into a chronic condition, akin to diabetes, that can be managed with a drug regimen — particularly if Trikafta is eventually approved for use in younger children and babies, before any lung damage has occurred. (It is initially approved for patients 12 and older.)

Patients who were unsure about whether they should bother attending college because they had always known they would die young are now being told they should think about planning for retirement.

Brian P. O’Sullivan, a pediatric pulmonologist at the Geisel School of Medicine at Dartmouth, who was not involved in either trial and has no financial ties to Vertex, said: “I’m in my 60s now, and I never thought I would see this day. It’s pretty amazing.”

Sarah Carollo, 28, a special needs teacher in Lee’s Summit, Mo., started Trikafta through a clinical trial in late 2018. Carollo feared she was heading into yet another hospitalization and might have to step away from the classroom where she teaches children with nonverbal autism. She couldn’t walk down a hallway without stopping to rest and catch her breath.

“As a person living with CF, my parents had been passing on to me this fear — we always had this constant fear of when the decline was going to happen, because we knew it was going to happen,” Carollo said.

A few days after she began taking the pill, her doctors tested her lung function and were so stunned at the improvement that they had to check whether they were really looking at the results from the right patient. Earlier this month, Carollo ran a 5K race with another patient, Laurana Blackburn, who was also taking the drug through the clinical trial.

“We felt like we had to honor what we had been given and show the capacity of what we had now,” Carollo said.

Cystic fibrosis has become a model for how to study, advocate for and develop drugs for other genetic diseases. The discovery of the gene in 1989 was a major scientific feat that helped persuade scientists and politicians to move forward with the $3 billion human genome project, Collins recalled. But that wasn’t just important to scientists.

On Aug. 25, 1989, an 8-year-old girl named Jenny wrote in her diary, “To Day is the most Best day ever in my Life They found a Jean for Cistik fibrosis.” Jenny McGlincy, now 38, was on vacation with her husband and daughter in Mexico when word began to circulate that the drug had been approved. She read the news on her phone and began crying.

McGlincy said she feels fortunate that she hasn’t been as sick as other people with cystic fibrosis, but she is eagerly awaiting the doctor’s appointment in a week and a half where she will find out the next steps to get access to the medication.

“We’ve finally reached the time that an improvement is possible,” McGlincy said.

“To think of my lung function improving or my digestion increasing, or even adding a few years to my life that I could spend with my daughter. … Now that it’s available, I’m a little like, ‘Is this really happening?’ ”

The therapy is a combination of three drugs that wouldn’t have been possible if scientists working in academic laboratories hadn’t unraveled the basic biology of the disease. Finding the gene was a needle-in-a-haystack-type problem, Collins said, and it led scientists to a malfunctioning protein that normally keeps the right balance of salt and water in the lungs.

There are more than 1,700 gene mutations that can cause the protein to malfunction, but in the most common mutation, the protein is misfolded and can’t reach the right spot in the cell — and even if it does reach that spot, it doesn’t work properly. The new combination therapy includes one drug that corrects the misfolded protein and two that activate the correctly folded protein when it reaches the right spot in the cell.

In the largest trial, reported in the New England Journal of Medicine, 403 patients who had at least one copy of the most common gene mutation underlying cystic fibrosis received either Trikafta or a placebo. There were improvements in objective tests of lung function, decreases in lung problems and hospitalizations and an increase in people’s quality of life.

Many physicians see the most transformative potential impact of the drug in the hope that it will be eventually approved for younger children, as Vertex’s other drugs have been over time.

The drug can help older patients, but it can’t erase years of lung damage; if it works and is safe in younger children, it could prevent damage in the first place.

“With treatments like this, we can actually anticipate that if a young child were started on this therapy, they could actually expect to have a normal life expectancy,” said Deepika Polineni, a pulmonologist at the University of Kansas Medical Center involved in the trial who has received consulting fees from Vertex.

“This is a breakthrough therapy for people with cystic fibrosis.”

Patients continued their maintenance therapy, such as coughing and using a vibrating vest, during the therapy — and future trials will test whether patients can reduce their dependence on the time-consuming regimen. Future research will also be needed to help the remaining 10 percent of patients, who have different gene mutations causing their disease.

Meghan McGarry, a pulmonologist at the University of California at San Francisco, recently completed a study that examined Puerto Rican and Dominican patients and found that their diseases were driven by rare mutations.

She said her concern is that the new drugs, as exciting as they are, will deepen health inequities, because those minority patients already have greater mortality than white patients with cystic fibrosis.

“It’s really heartbreaking for the patients who don’t qualify. I think it’s really hard to celebrate with a portion of your patients and have other patients where you know they don’t have that. We had a mom who said, ‘Those drugs aren’t for our people,'” McGarry said.

She noted that when some of Vertex’s early drugs came out and helped a small population of patients, it gave others in the community hope because it foreshadowed the development of better drugs that would work for more people.

“Now, when the majority of patients already have it,” she said, they ask: “When is it my child’s turn? And is that going to come?”

It also remains to be seen whether patients have an easy time gaining access to the drug, which will cost $311,000 a year. While that is a tremendous amount, orphan drugs for small patient populations typically carry very large price tags, and physicians are optimistic that insurers will cover the drug.

For now, the cystic fibrosis community will be celebrating. Collins said that after he discovered the gene behind the illness in 1989, he wrote a song called “Dare to Dream” about the hope for a treatment. He plans to sing it at the meeting.

When he wrote the song, “we had the gene, but it wasn’t clear how it would get us to this kind of outcome,” Collins said. “We’re going to do that again on Friday morning, with 3,000 people, and I’m probably going to cry.”

2019 © The Washington Post

This article was originally published by The Washington Post.

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