Tag: 14/7/23

Categories : Immune SystemTags : Leave a comment

Adaptive Immune Memory Resides in the Shape of DNA

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Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

One of the adaptive immune system’s most intriguing abilities of the is its memory: upon first contact with antigens, it takes around two weeks to respond, but responses afterwards are much faster, as if the cells ‘remembered’ the antigen. But how is this memory attained? In a recent publication in Science Immunology, a team of researchers examined epigenetic and the structure of DNA for possible clues.

In their research paper, first author Anne Onrust-van Schoonhoven and colleagues compared the response of immune cells that had never been in contact with an antigen (called naïve cells) with cells previously exposed to antigen (memory cells) and sort of knew it. They focused on the differences in the epigenetic control of the cellular machinery and the nuclear architecture of the cells, two mechanisms that could explain the quick activation pattern of memory cells.

While all the cells in an individual have the same genetic information, different cell types access to different parts of the DNA. The term ‘epigenetics’ encompasses the mechanisms that dynamically control this access. The results revealed a particular epigenetic signature in memory T helper (TH)2 cells, resulting in the rapid activation of a crucial set of genes compared to naïve cells. These genes were much more accessible to the cellular machinery, in particular to a family of transcription factors called AP-1. Like athletes before a race, these genes had essentially been ‘warming up’ ever since the cell’s first contact with the antigen.

However, this epigenetic signature was just the tip of the iceberg. It is known that the position of the DNA in the nucleus is not random and reflects the cell’s activation state. The researchers found that, indeed, the 3D distribution of DNA in the nucleus is different between naïve and memory immune cells. Key genes for the early immune response are grouped together and under the influence of the same regulatory regions, called enhancers. Keeping with the racing metaphor, the genes are not only warmed-up, but also gathered together at the starting line.

Although most of the research has focused on healthy cells, the scientific team wondered whether any of the mechanisms found could, when altered, explain actual diseases in which the immune system plays an important role. To address this question, they analysed immune cells from chronic asthma patients and found that the circuits identified as key for an early and strong immune response were overactivated.

The epigenetic control of the immune system is a blossoming field and discoveries like the ones by Dr Stik and colleagues are setting the stage for the next generation of epigenetic drugs and treatments, targeting autoimmune diseases and cancer.

Source: Josep Carreras Leukaemia Research Institute

Categories : HospitalsTags : Leave a comment

Staff at Chatsworth Hospital Picket over Poor Working Conditions

On By ModernMedia
Staff, including nurses, at RK Khan Hospital in Chatsworth, Durban, picketed on Wednesday over poor working conditions at the facility. Photo: Tsoanelo Sefoloko

By Tsoanelo Sefoloko

Nurses, administration staff and general workers brought parts of RK Khan Hospital in Chatsworth, Durban, to a standstill for about an hour on Wednesday. They protested outside the hospital to highlight what they say are poor working conditions. 

Protesting nurses say they are forced to perform cleaning duties in addition to patient care because the hospital has not employed enough cleaners. Other workers complained of staff shortages in the administration and general units.

Workers say they met with the management in February. Union leaders had asked the facility to commit to resolving their complaints.

Nurse Zizakele Ndlovu said they were told by the union leaders that working conditions would improve. But nothing changed, she said.

“The conditions we work under at the hospital are not good. We end up having to work more hours, and we don’t get paid for overtime. Sometimes I even work as a clerk,” she said.

“The department treats us as if we don’t know our job, and we don’t deserve what we are asking for. We lost many workers to Covid; some retired and others resigned. Those vacancies have not been filled. Even at top management there are lots of vacancies and this leads to poor service.”

Chairperson at the hospital of the National Education, Health and Allied and Workers’ Union (NEHAWU) David Mpongose said they had engaged management and had been promised that the situation would improve.

“Our bosses are arrogant. They really don’t take us seriously. Each time they make empty promises, so we decided to protest for the provincial government to assist us,” said Mpongose.

Xolani Mnguni, a cleaner, said he earned R7800 per month under the hospital’s previous contractor, but now only earns R3000 under the current contractor. He also said he has to do jobs other than cleaning.

Hospital CEO Linda Sobekwa accepted the workers’ memorandum and signed it on behalf of the provincial health department. She promised to ensure that the department responded within ten days as requested.

Agiza Hlongwane, spokesperson for the KwaZulu-Natal Department of Health, said officials would consider the workers’ demands and respond to them.

Republished under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Ophthalmology PaediatricsTags : Leave a comment

Atropine Eyedrops Fail to Slow Myopia Progression in US Children

On By ModernMedia
Photo by Jeffrey Riley on Unsplash

Use of low-dose atropine eyedrops (concentration 0.01%) was no better than placebo at slowing myopia progression and elongation of the eye among children treated for two years, according to a randomised controlled trial conducted in the US. The trial aimed to identify an effective way to manage this leading and increasingly common cause of refractive error, which can cause serious uncorrectable vision loss later in life. Results from the trial, published in JAMA Ophthalmology, contradict those from recent trials in East Asia.

The study was conducted by the Pediatric Eye Disease Investigator Group (PEDIG) and funded by the National Eye Institute (NEI).

“The overall mixed results on low-dose atropine show us we need more research. Would a different dose be more effective in a US population? Would combining atropine with other strategies have a synergistic effect? Could we develop other approaches to treatment or prevention based on a better understanding of what causes myopia progression?” said Michael F. Chiang, MD, director of the NEI, which is part of the National Institutes of Health.

Identifying an optimal approach for preventing high (advanced) myopia is urgently needed given the escalating prevalence of myopia overall and the risk of it progressing to high myopia. By 2030, it’s predicted that 39 million people in the U.S. will have myopia. By 2050, that number is expected to grow to 44 million in the U.S. and to 50% of the global population.

Much stronger concentrations of atropine eyedrops (0.5-1.0%) have long been used by pediatric eye doctors to slow myopia progression. While effective, such doses cause light sensitivity and blurry near vision while on the nightly eyedrops. Thus, there is interest in clinical studies assessing lower concentrations that have been shown to have fewer side effects.

“The absence of a treatment benefit in our US-based study, compared with East Asian studies, may reflect racial differences in atropine response. The study enrolled fewer Asian children, whose myopia progresses more quickly, and included Black children, whose myopia progresses less quickly compared with other races,” noted the study’s lead co-author, Michael X. Repka, M.D., professor of ophthalmology, Johns Hopkins University.

For the study, 187 children ages 5 to 12 years with low-to-moderate bilateral myopia were randomly assigned to use nightly atropine (0.01%) (125 children) or placebo (62 children) eyedrops for two years. Study participants, their parents, and the eye care providers were masked to the group assignments.

After the treatment period, and 6 months after treatment stopped, there were no significant differences between the groups in terms of changes in degree of myopia compared with baseline. Nor were there significant differences in axial length within the two groups when compared with baseline measurements.

“It’s possible that a different concentration of atropine is needed for US children to experience a benefit,” noted the study’s other lead co-author, Katherine K. Weise, OD, professor, University of Alabama at Birmingham. “Clinical researchers could evaluate new pharmaceuticals and special wavelengths of light in combination with optical strategies, like special glasses or contact lenses, to see what works in reducing the progression of myopia.”

Among children, myopia will stabilise in about half of children around age 16 years, and among an increasingly larger percentage as they get older. By their early twenties, about 10% of individuals with myopia will continue to grow more nearsighted, and by age 24 years that percentage is 4%.

“Vision scientists may help us figure out what’s different about the myopic eye, even among different races and ethnicities, to help create new treatment strategies,” she said. It will take a real convergence of eye research to solve the environmental, genetic, and structural mystery of myopia.”

Source: NIH/National Eye Institute

Categories : Ethics and Law Surgeries & ProceduresTags : Leave a comment

Plastic Surgeon Loses Medical Licence for Streaming Surgeries on TikTok

On By ModernMedia
Photo by Piron Guillaume on Unspalsh

A plastic surgeon in the US has had her medical licence permanently revoked for livestreaming parts of her surgeries and causing harm to her patients while doing so, according to the Washington Post.

Dr Katherine Grawe, who was also fined US$4500, streamed her operations with between 100 000 and 500 000 viewers at a time, speaking to the camera and on occasion answering viewers’ questions.

Three of her patients whose surgeries she had streamed experienced complications – infections, a perforated intestine and a loss of brain function – that required further medical care. She told the Washington Post that she did not believe that her livestreaming her surgeries had resulted in harm to her patients.

“Nobody wants a complication, and we never want things to go poorly, but any complications that happened with me were not because I was not paying attention,” Grawe said. “My whole goal in life is to give these people confidence and make them more beautiful. And, unfortunately, they suffered these complications, and I feel very sad for them. I would never want anything bad to happen to them.”

She specialised in cosmetic surgery for women’s breasts, as well as tummy tucks and other procedures, Grawe said. She is also being sued by the three patients who had complications. Since she started practising in 2010 with her Dr Roxy practice, she built up a social media following and eventually began livestreaming on TikTok in an effort to break down “this scary wall” between patients and doctors. Her patients all signed consent forms for their procedures to be livestreamed.

Grawe’s licence was suspended in November, and she pleaded with the board, saying that she would never livestream her surgeries again. The board was not moved by her appeal. “Dr Grawe’s social media was more important to her than the lives of the patients she treated,” the board stated.

The board had warned her in 2018 over patient confidentiality concerns in her livestreaming, and again in 2021.

Surgeries conducted in front of an audience are nothing new in medicine; medical students and clinicians alike observe procedures to learn and share knowledge. Some operating theatres are specially designed to host audiences behind windows overlooking the operating table. In the 21st century, it has become commonplace for educational livestreaming of surgeries, with considerable benefits for surgeons and increased anatomy knowledge scores.

There is also some evidence of risks to patients: one review found no increased risk of harm in urology, but this was not true for other surgical fields. Thirteen

Unlike in-person viewing of surgeries, data protection considerations must be employed as operating on a patient often may reveal identifiable information even if not livestreaming to a wide audience. Certain video conferencing platforms may not be secure, and recordings of the procedure may inadvertently be accessible to others, eg being stored on network drives, on the cloud without password protection and so on. There are secure communication apps that can be used to confidentially view and share patient data, such as TigerConnect, Medic Bleep, Forward Health and Siilo.

Categories : NeurologyTags : Leave a comment

Simple Oxygen Therapy can Boost Motor Skills Rehabilitation

On By ModernMedia
Photo by Samuel Ramos on Unsplash

Scientists studying the impact of oxygen supplementation on motor learning have found a promising treatment that could help patients who have experienced neurological trauma recover lost motor skills.

“A simple and easy to administer treatment with 100% oxygen can drastically improve human motor learning processes,” said Dr Marc Dalecki, now at the German University of Health and Sports in Berlin, senior author of the study in Frontiers in Neuroscience.

Repurposing a frontline treatment

Brains have a high oxygen demand, and hypoxia causes cognitive function to decrease, while in high-oxygen contexts it recovers, and the delivery of 100% oxygen is already used to help preserve as much of the brain as possible in patients with neurological injuries.

Motor learning is particularly dependent on oxygen-reliant information processing and memory functions: humans learn by trial and error, so the ability to remember and integrate information from previous trials is critical to efficient and effective motor learning. So could supplementing oxygen while learning a motor task help people learn faster and more effectively, offering hope for neurorehabilitation patients?

“I had this idea in my mind for almost a decade and promised myself to investigate it once I got my own research lab,” said Dalecki, who led the experimental research at the School of Kinesiology at Louisiana State University. “And with Zheng Wang, now Dr Zheng Wang, I had the perfect doctoral student to run it – a keen physiotherapist with a clinical background and stroke patient experience.”

Hand-eye coordination

Dalecki and Wang recruited 40 participants, 20 of whom received 100% oxygen at normobaric pressure and 20 of whom received medical air (21% oxygen) through a nasal cannula during the “adaptation” or learning phase of a task.

Dalecki and Wang selected a simple visuomotor task which involved drawing lines between different targets on a digital tablet with a stylus. The task was designed to test how quickly the participants were able to integrate information from the eye and hand, a crucial part of motor learning. After the task had been learned, the alignment of the cursor and the stylus was altered to see how effectively the participants adapted to the inconsistency, and then realigned for a final session to see how they adapted to the realignment.

“The oxygen treatment led to substantially faster and about 30% better learning in a typical visuomotor adaptation task,” said Wang, first author of the study and now at the Mayo Clinic in Rochester. “We also demonstrate that the participants were able to consolidate these improvements after the termination of the oxygen treatment.”

Oxygen improved learning by 30%

The scientists found that the participants who had received oxygen learned faster and performed better, improvements which extended into later sessions of the task when oxygen was not administered.

The oxygen group moved the pen more smoothly and more accurately, and when the cursor was adjusted in a deliberate attempt to throw them off, they adapted more quickly. They also made bigger mistakes when the alignment of the stylus was corrected, suggesting they had integrated the previous alignment more thoroughly than the other group.

Dalecki and Wang plan to investigate the long-term effects of this supplementation on learning and test the intervention with other motor learning tasks: it is possible that the relevant brain functions for this task in particular benefit from high ambient oxygen levels, leading to the observed advantages in performance. They also hope to bring the oxygen treatment to elderly and injured people, in the hope that it will help them re-learn motor skills.

“Our future plan is to investigate whether this treatment can also improve motor recovery processes following brain trauma,” said Dalecki. “Since it worked in the young healthy brain, we expect that the effects may even be larger in the neurologically impaired, more vulnerable brain.”

Source: Medical Xpress