Tag: 16/4/21

Human-monkey Chimeric Embryos Set off Ethics Debate

Blastocyst. Source: Wikimedia Commons.

A study published in the journal Cell has announced the creation of human-monkey chimeric embryos, igniting renewed debate over ethics.

The embryos are known as chimeras, organisms whose cells come from two or more “individuals”, and in this case, different species: a long-tailed macaque and a human. The research confirmed that the cells can survive and multiply.

Natural human chimeras do exist, and can involve humans cells from two embryos in the same womb fusing to produce a single individual, or a combination of maternal and foetal cells, or monozygotic twins sharing blood cells from a shared placenta.

Previously, researchers had produced pig or sheep embryos that contained human cells, in an effort to one day develop a way to grow human organs for transplant inside the animals.

The researchers, led by Prof Juan Carlos Izpisua Belmonte from the Salk Institute in the US, said that the results shed new light on the communications pathways between cells of different species. This could help with future efforts to engineer chimeras using more distantly related species.

“These results may help to better understand early human development and primate evolution and develop effective strategies to improve human chimerism in evolutionarily distant species,” the authors wrote.

In 2019, the Spanish newspaper El País reported on rumours that a team of researchers led by Belmonte had created monkey-human chimeras.

Specific human foetal cells called fibroblasts were reprogrammed to become stem cells, and were then introduced into 132 embryos of long-tailed macaques, six days after fertilisation.

“Twenty-five human cells were injected and on average we observed around 4% of human cells in the monkey epiblast,” said Dr Jun Wu, a co-author of the research, and now at the University of Texas Southwestern Medical Center.

The embryos were grown in petri dishes and were terminated 19 days after the stem cells were injected. The human cells were engineered with a fluorescent protein to enable identification.

The researchers reported that 132 embryos contained human cells on day seven after fertilisation. However, the proportion containing human cells fell over time.

“We demonstrated that the human stem cells survived and generated additional cells, as would happen normally as primate embryos develop and form the layers of cells that eventually lead to all of an animal’s organs,” Belmonte said.

The researchers also found differences in intercellular interactions between human and monkey cells within chimeric embryos, compared to the normal monkey embryos.

The researchers hoped the research would help develop “transplantable human tissues and organs in pigs to help overcome the shortages of donor organs worldwide”, said Wu.

Prof Robin Lovell-Badge, a developmental biologist from the Francis Crick Institute in London, said at the time of the El País report he was not concerned about the ethics of the experiment, noting the team had only produced a ball of cells. But he noted conundrums could arise in the future should the embryos be allowed to develop further.

While not the first attempt at making human-monkey chimeras – another group reported such experiments last year – the new study has reignited such concerns. Prof Julian Savulescu, the director of the Oxford Uehiro Centre for Practical Ethics and co-director of the Wellcome Centre for Ethics and Humanities at the University of Oxford, said the research had raised all sorts of ethical concerns.

“These embryos were destroyed at 20 days of development but it is only a matter of time before human-nonhuman chimeras are successfully developed, perhaps as a source of organs for humans,” he said, and added that a key ethical concern was the moral status of such organisms.

“Before any experiments are performed on live-born chimeras, or their organs extracted, it is essential that their mental capacities and lives are properly assessed. What looks like a nonhuman animal may mentally be close to a human,” he said. “We will need new ways to understand animals, their mental lives and relationships before they are used for human benefit.”

Others were less concerned, and rather pointed out that all the study found was that the creation of such chimera was simply ineffective.

Dr Alfonso Martinez Arias, an affiliated lecturer in the department of genetics at the University of Cambridge, said: “I do not think that the conclusions are backed up by solid data. The results, in so far as they can be interpreted, show that these chimeras do not work and that all experimental animals are very sick.

“Importantly, there are many systems based on human embryonic stem cells to study human development that are ethically acceptable and in the end, we shall use this rather than chimeras of the kind suggested here.”

Source: The Guardian

Experts Urge a Re-think on Olympic Games

With 100 days remaining until the Tokyo Olympic and Paralympic games, experts urge that the organisers must urgently reconsider plans to hold the games this summer.

Writing in The BMJ, Kazuki Shimizu at the London School of Economics and Political Science and colleagues said that the trajectory of the pandemic is still highly uncertain, warning that international mass gathering events such as Tokyo 2020 “are still neither safe nor secure”.

They say instead that “we must accelerate efforts towards containing and ending the pandemic by maintaining public health and social measures, promoting behavior change, disseminating vaccines widely, and strengthening health systems.”

While considerable scientific advancements have taken place over the past year, they said that vaccine roll-out has been inequitable, with many low and middle income countries having reduced access.

While a special scheme for vaccinating athletes orchestrated by the Olympics Organising Committee may help save lives, they argued that “it could also encourage vaccine diplomacy, undermine global solidarity (including the Covax global access scheme), and promote vaccine nationalism.”

Another concern that they highlighted was the fact that Japan, unlike neighbouring countries in the Asia-Pacific region, still has not achieved COVID containment.

“Even healthcare workers and other high risk populations will not have access to vaccines before Tokyo 2020, to say nothing of the general population,” they write.

In order to effectively protect participants from COVID, “Japan must develop and implement a clear strategy to eliminate community transmission within its borders, as Australia did before the Australian Open tennis tournament.”

Japan and the International Olympic Committee must also agree to operational plans based on robust science and share them with the international community, they added.

Waiving quarantine for incoming athletes, officials, broadcasters, press, and marketing partners “risks importing and spreading covid-19 variants of concern” and while international spectators will be excluded from the games, “cases could rise across Japan and be exported globally because of increased domestic travel – as encouraged by Japan’s official campaigns in 2020.”
However, a recent survey indicated that 70% of Japanese would not want to attend the Olympic Games, due to COVID.

An overwhelmed healthcare system combined with an ineffective test trace and isolate scheme “could seriously undermine Japan’s ability to manage Tokyo 2020 safely and contain any outbreak caused by mass mobilization,” they write.

They also highlight the fact that there has been very little about the Paralympic games through official channels, and how the health and rights of disabled people will be protected during international competition.
“The whole global community recognizes the need to contain the pandemic and save lives. Holding Tokyo 2020 for domestic political and economic purposes – ignoring scientific and moral imperatives – is contradictory to Japan’s commitment to global health and human security,” they argued.

“We must reconsider this summer’s games and instead collaborate internationally to agree a set of global and domestic conditions under which international multisport events can be held in the years ahead. These conditions must embody both Olympic and Paralympic values and adhere to international principles of public health,” they concluded.

Source: News-Medical.Net

Journal information: Shimizu, K., et al. (2021) Reconsider this summer’s Olympic and Paralympic games. BMJ. doi.org/10.1136/bmj.n962.

Encapsulated Clusters of Noroviruses are Resistant to Disinfection

Encapsulated clusters of noroviruses which can cause stomach flu have been found to be resistant to detergent and ultraviolet disinfection.

Noroviruses are the leading cause of gastroenteritis around the world, with more than 21 million cases annually in the United States. The findings of this study show that there is a need to revise current disinfection, sanitation and hygiene practices which serve to protect against infection with noroviruses.

In 2018, the research team had found that noroviruses can be transmitted to humans in the form of membrane-enclosed packets that contain clusters of viruses. Previously, it was thought that viruses spread via exposure to individual virus particles, but the 2018 study, , showed how membrane-enclosed clusters arrive at a human cell and release a large number of viruses.

For the new study, Drs Danmeng Shuai, Nihal Altan-Bonnet and the study’s first author Mengyang Zhang, a doctoral student co-advised through a GW/NIH Graduate Partnerships Program, examined how such protected virus clusters behave in the environment. They found that the virus clusters could survive disinfection attempts with detergent solutions or even UV light. Water treatment plants use UV light to kill noroviruses and other pathogens, and is being widely used in the COVID pandemic.

“These membrane-cloaked viruses are tricky,” explained study co-author Danmeng Shuai, PhD, associate professor of civil and environmental engineering, George Washington University. “Past research shows they can evade the body’s immune system and that they are highly infectious. Our study shows these membrane enclosed viruses are also able to dodge efforts to kill them with standard disinfectants.”

“We have to consider these viral clusters cloaked in vesicle membranes as unique infectious agents in the public health arena,” added Nihal Altan-Bonnet, PhD, a senior investigator and the head of the Laboratory of Host-Pathogen Dynamics at the National Heart, Lung, and Blood Institute. “When it comes to virulence -; and now with this study, disinfection and sanitation -; the sum is much more than its parts. And these clusters are endowed with properties that are absent from other types of viral particles.”

Future studies are needed to determine whether certain kinds of cleaning solutions or more UV light exposure would degrade the protective membrane and/or kill the viruses inside. Such research would hopefully come up with improved disinfection methods that could be used for cleaning surfaces in the home, in restaurants and in places where norovirus can spread and cause outbreaks, like cruise ships.

“Our study’s findings represent a step towards recommendations for pathogen control in the environment, and public health protection,” Dr Altan-Bonnet said.

Source: News-Medical.Net

Journal information: Zhang, M., et al. (2021) Emerging Pathogenic Unit of Vesicle-Cloaked Murine Norovirus Clusters is Resistant to Environmental Stresses and UV254 Disinfection. Environmental Science and Technology. doi.org/10.1021/acs.est.1c01763.

Scientists Crack Neuron Information Storage Code

A team of scientists from the UK and Australia have discovered that single neurons can store electrical patterns, similar to memories. This represents a breakthrough towards solving how neural systems are able to process and store information.

By comparing predictions from mathematical modeling to lab-based experiments with mammalian neurons, they were able to determine how different parameters, such as how long it takes for neuronal signals to be processed and how sensitive a cell is to external signals, affect how neural systems encode information.

The research team found that a single neuron is able to select between different patterns, dependent on the properties of each individual stimulus, for example slight differences in stimulation timing resulted in the emergence of no electrical activity spikes, single spikes per delay or two spikes per delay,

By opening up new avenues into research on the encoding of information in the brain and how this relates to memory formation, the study could also allow new insights into the causes and treatments of mental health conditions such as dementia.

“This work highlights how mathematical analysis and wet-lab experiments can be closely integrated to shed new light on fundamental problems in neuroscience,” said Dr Wedgwood. “That the theoretical predictions were so readily confirmed in experiments gives us great confidence in the mathematical approach as a tool for understanding how individual cells store patterns of activity. In the long run, we hope that this is the first step to a better understanding of memory formation in neural networks.”

Professor Krauskopf from the University of Auckland remarked, “The research shows that a living neuron coupled to itself is able to sustain different patterns in response to a stimulus. This is an exciting first step towards understanding how groups of neurons are able to respond to external stimuli in a precise temporal manner.”

“Communication between neurons occurs over large distances. The communication delay associated with this plays an important role in shaping the overall response of a network. This insight is crucial to how neural systems encode memories, which is one of the most fundamental questions in neuroscience,” added Professor Tsaneva from the University of Exeter’s Living Systems Institute.

Source: Medical Xpress

Journal information: Kyle C. A. Wedgwood et al, Robust spike timing in an excitable cell with delayed feedback, Journal of The Royal Society Interface (2021). dx.doi.org/10.1098/rsif.2021.0029

Energy Drinks Linked to Heart Failure in Young Man

In the journal BMJ Case Reports, doctors have warned that heavy energy drink consumption may be linked to heart failure, after treating a 21 year old man who had drunk 2 litres of the drinks every day for 2 years.

This report adds to the growing body of published evidence on, and mounting concerns about, the potential heart harms of these drinks, the authors stated.

The young man in the case report experienced 4 months of progressive shortness of breath on exertion, breathlessness while lying down (orthopnoea), and weight loss before ending up in intensive care.

He habitually drank an average of four 500 ml cans of energy drink every day: each can contains 160 mg of caffeine plus taurine (a protein included in energy drinks for its cytoprotective benefits) and various other ingredients. He said he had been doing this for around 2 years. In the past he had also suffered bouts of indigestion, tremor and palpitations for which he hadn’t sought medical help. In the 3 months before he was admitted to hospital, he had discontinued his university studies because he was feeling so unwell and lethargic.

Testing revealed heart and kidney failure, both of which were severe enough to consider putting him on the list for a dual organ transplant. The kidney failure was due to an unrelated condition.

However, his heart symptoms and function improved significantly with drug treatment and after he cut out energy drinks completely. “However, it is difficult to predict the clinical course of recovery or potential for relapse,” caution the authors.

The authors noted that besides this case report, there have been several others as well as review articles that have highlighted mounting concerns about the potential cardiovascular system harms of energy drinks.

The authors theorised that one factor may be caffeine overstimulating the sympathetic nervous system; energy drinks are also known to increase blood pressure and can trigger heart rhythm abnormalities.

“Clear warnings should be provided about the potential cardiovascular dangers of energy drink consumption in large amounts,” the authors concluded.

“I think there should be more awareness about energy drinks and the effect of their contents,” added the subject of this case report. “I believe they are very addictive and far too accessible to young children.”

Source: Medical Xpress

Journal information: Case report: Energy drink-induced cardiomyopathy, BMJ Case Reports (2021). DOI: 10.1136/bcr-2020-239370

Black Barbershops with Pharmacist-led Care can Combat Hypertension

Black and white image of a black man getting a haircut at a barbershop. Credit: BariKive from Pexels.

Black barbershops with pharmacist-led blood pressure (BP) care for their clients, have been shown to be cost effective, with the high initial costs offsetting reduced cardiovascular events later in life.

The study cost simulations were based on the original  Los Angeles Barbershop Blood Pressure Study (LABBPS). In that study, intervention consisted of a trial with men being assigned either to barbershops where barbers encouraged patrons to meet with pharmacists who prescribed drug therapy under an agreement with the participants’ doctors, with the control group being men assigned to barbershops where the barbers only promoted lifestyle modification and physician visits. This intervention resulted in a mean BP drop of 27.0mmHg compared to the control group which fell by 9.3mmHg.

In a 1-year intervention based on costs for the LABBPS, on average, $2356 more per participant than the controls and was associated with a gain of 0.06 quality-adjusted life years (QALYs) over a 10-year horizon, according to Brandon Bellows, PharmD, MS, of Columbia University in New York City, and colleagues.

Thus, in computer simulations,  the LABBPS intervention was associated with 10-year projected total healthcare costs averaging $42 717 per QALY gained, reported the researchers.

“One concern raised as a potential barrier to widespread LABBPS implementation is the specialty training of clinical pharmacists. In this analysis, the cost of specialty training and certification was included; the results suggest that long-term health benefits and avoided healthcare costs of the LABBPS offset these upfront training costs,” the researchers wrote.

The team reported that the cost effectiveness of the intervention could be increased under various various scenarios:

  • Only using generic drugs: $17 162 per QALY gained
  • Shortening intervention to 26 weeks: $18 300 per QALY gained
  • Implementing optimal savings from less time spent on intervention tasks, lower equipment costs, only using generics, and no participant incentive costs: intervention becomes dominant (both less expensive and more effective than control)

However, if pharmacists were less likely to intensify antihypertensive medications when systolic BP was ≥ 150 mm Hg, or if pharmacists took longer to get to the barbershops, the cost of the LABBPS intervention would exceed $50 000 per QALY gained.

“Hypertension care delivered by clinical pharmacists in Black barbershops is a highly cost-effective way to improve BP control in Black men,” the authors concluded.  

The LABBPS has received praise for demonstrating that Black men with uncontrolled hypertension had better BP control after 6 months with barbershop visits by specialty pharmacists than with regular physician visits. Extending the intervention to 1 year did not change the results.

Researchers previously reported that a telemedicine component could bring down cost and maintain efficiency of the LABBPS program.

“Hypertension prevalence remains higher among non-Hispanic Black men than in any other racial or ethnic group in the US. Hypertension awareness and treatment have plateaued in the US since 2010, and Black men continue to have worse BP control and higher hypertension-related cardiovascular disease mortality rates compared with other groups,” the investigators wrote.

The researchers assumed that after the one-year intervention period, processes of hypertension care management returned to standard care, which was a major limitation of the study.

“These findings may also be somewhat limited in scope as a healthcare sector perspective was used, which only considers direct healthcare costs, rather than a societal perspective, which may include indirect costs such as improvements in productivity,” noted Bellows and co-authors. “Finally, cost-effectiveness estimated for the LABBPS may not be generalizable to other U.S. communities, as it was specific to Los Angeles County and was driven in part by the high underlying risk of cardiovascular disease in Black men.”

Source: MedPage Today

Journal information: Bryant KB, et al “Cost-effectiveness of hypertension treatment by pharmacists in black barbershops” Circulation 2021; DOI: 10.1161/CIRCULATIONAHA.120.051683.