Day: June 3, 2021

Tiny Implant Shelters Diabetes-curing Cells

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A team of researchers have developed a miniscule device that allows them to implant insulin-secreting cells into diabetic mice, which secrete insulin in response to blood sugar without being destroyed by the immune system.

The findings are published in the journal Science Translational Medicine.

“We can take a person’s skin or fat cells, make them into stem cells and then grow those stem cells into insulin-secreting cells,” said co-senior investigator Jeffrey R Millman, PhD, an associate professor of medicine at Washington University. “The problem is that in people with Type 1 diabetes, the immune system attacks those insulin-secreting cells and destroys them. To deliver those cells as a therapy, we need devices to house cells that secrete insulin in response to blood sugar, while also protecting those cells from the immune response.”

Prof Millman, also an associate professor of biomedical engineering, had previously developed and honed a method to make stem cells and then grow them into insulin-secreting beta cells. Prof Millman previously used those beta cells to reverse diabetes in mice, but it was not clear how the insulin-secreting cells might safely be implanted into people with diabetes.

Prof Millman explained why the new device’s structure was so important.

“The device, which is about the width of a few strands of hair, is micro-porous—with openings too small for other cells to squeeze into—so the insulin-secreting cells consequently can’t be destroyed by immune cells, which are larger than the openings,” he said. “One of challenges in this scenario is to protect the cells inside of the implant without starving them. They still need nutrients and oxygen from the blood to stay alive. With this device, we seem to have made something in what you might call a Goldilocks zone, where the cells could feel just right inside the device and remain healthy and functional, releasing insulin in response to blood sugar levels.”

Millman’s laboratory collaborated with researchers from the laboratory of Minglin Ma, PhD, an associate professor of biomedical engineering at Cornell and the study’s other co-senior investigator. Prof Ma has been working to develop biomaterials that can help implant beta cells safely into animals and, eventually, people with Type 1 diabetes.

In recent years a number of implants have been tried to varying degrees of success. For this study, the team led by Prof Ma developed a nanofibre-integrated cell encapsulation (NICE) device. They filled those implants with insulin-secreting beta cells grown from stem cells and then implanted the devices into the abdomens of diabetic mice.

“The combined structural, mechanical and chemical properties of the device we used kept other cells in the mice from completely isolating the implant and, essentially, choking it off and making it ineffective,” Prof Ma explained. “The implants floated freely inside the animals, and when we removed them after about six months, the insulin-secreting cells inside the implants still were functioning. And importantly, it is a very robust and safe device.”

The cells in the implants continued to secrete insulin and control blood sugar in the mice for up to 200 days — even without any immunosuppressive drugs being administered.
“We’d rather not have to suppress someone’s immune system with drugs, because that would make the patient vulnerable to infections,” Prof Millman said. “The device we used in these experiments protected the implanted cells from the mice’s immune systems, and we believe similar devices could work the same way in people with insulin-dependent diabetes.”

Profs Millman and Ma stress that a considerable amount of work is needed before the device can be trialled in a clinical setting.

Source: Washington University School of Medicine in St Louis

Journal information: X. Wang et al., “A nanofibrous encapsulation device for safe delivery of insulin-producing cells to treat type 1 diabetes,” Science Translational Medicine (2021)

Stronger Immune Systems in Women Protect against Skin Cancer

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Women may have a stronger immune response to a common form of skin cancer than men, according to a preliminary study on mice and human cells.

Men develop more skin squamous cell carcinoma (cSCC) than females and their tumours are more aggressive, though it is not clear if this is related to sunlight exposure. Using mouse models to answer the question, they found that male mice developed more aggressive tumours than females, despite receiving identical treatments.

In female mouse skin and tumours, the immune cell infiltration and gene expression related to the anti-cancer immune system were increased, suggesting a protective effect of the immune system.

In keeping with the animal study, 931 patient records collected from four hospitals in Manchester, London and France, the researchers identified that while women commonly have a more mild form of cSCC compared to men, immunocompromised women developed cSCC in a way more similar to men

That suggests the protective effect of their immune system may have been compromised.

These results were confirmed in a further cohort of sun-damaged skin from the US. In this cohort, human epidermal cells confirmed women’s skin activated immune-cancer fighting pathways and immune cells at sites damaged by sunlight.

The US cohort also that showed CD4 and CD8 T cells, which are important in our immune response to skin cancer, were twice as abundant in women as in men.

The researchers used RNA sequencing to examine differences in male and female immunosuppressed mice and human skin cells.

“It has long been assumed that men are at higher risk of getting non-melanoma skin cancer than women” said Dr Amaya Viros, from The University of Manchester.

“Other life-style and behavioural differences between men, such as the type of work or exposure to the sun are likely to be significant.

“However, we also identify for the first time the possible biological reasons, rooted in the immune system, which explains why men may have more severe disease.

“Although this is early research, we believe the immune response is sex-biased in the most common form of skin cancer, and highlights that female immunity may offer greater protection than male immunity.”

Dr Viros added: “We can’t yet explain why women have a more nuanced immune system than men.

“But perhaps it’s reasonable to speculate that women’s evolutionary ability to carry an unborn child of foreign genetic material may require their immunological system to be very finely tuned and have unique skills.

“Very little is known about how sex differences affect incidence and outcome in infectious diseases, autoimmune disorders and cancer. More work needs to be done. But we feel this study has opened a window into this area, and could one day have important implications on other types of immunologically based diseases.

“And it suggests if doctors are to offer personalised treatment of cancer, then biological sex should be one of the factors they take into account.”

Commenting on the study, Dr Samuel Godfrey, Research Information Manager at Cancer Research UK said: “Research like this chips away at the huge question of why people respond to cancer differently. Knowing more about what drives immune responses to cancer could give rise to new treatment options and show us a different perspective on preventing skin cancer.”

Source: Medical Xpress

Journal information: Timothy Budden et al, Female Immunity Protects from Cutaneous Squamous Cell Carcinoma, Clinical Cancer Research (2021). DOI: 10.1158/1078-0432.CCR-20-4261

Tobacco Industry Linked to Disproven COVID ‘Protective Effect’ of Nicotine

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An investigation by The BMJ uncovered undisclosed financial links between certain authors and the tobacco and e-cigarette industry in a number of COVID research papers, which had suggested that smokers were less likely to develop COVID. 

In April 2020, two French studies (in preprint and not yet peer reviewed) suggested that nicotine might have a protective effect against COVID, which was coined the ‘nicotine hypothesis’.

The studies were reported on widely by the media, causing fears that it could undermine decades of tobacco control. What should have been an opportunity for promoting cessation of this practice which every year kills five million people around the world.

Since then, the ‘nicotine hypothesis’ has been soundly disproved, with several studies showing that, to the contrary, smoking is associated with an increased chance of COVID related death.

Journalists Stéphane Horel and Ties Keyze investigated the circumstances of these reports. They pointed out that one of the study authors, Professor Jean-Pierre Changeux, has a history of receiving funding from the Council for Tobacco Research, whose purpose was to fund research that would cast doubt on the dangers of smoking and focus on the positive effects of nicotine.

From 1995 to 1998, documents from the tobacco industry show that Changeux’s laboratory received $220,000 (£155,000; €180,000) from the Council for Tobacco Research.

When approached by The BMJ, Changeux assured them that he has not received any funding linked “directly or indirectly with the tobacco industry” since the 1990s.

In late April 2020, Greek researcher Konstantinos Farsalinos was the first to publish the ‘nicotine hypothesis’ formally in a journal, in an editorial in Toxicology Reports.

That journal’s editor in chief, Aristidis Tsatsakis was a co-author, as was A Wallace Hayes, who in 2013 had been a member of Philip Morris International’s scientific advisory board, and had served as a paid consultant to the tobacco company.

Another co-author is Konstantinos Poulas, head of the Molecular Biology and Immunology Laboratory at the University of Patras, where Farsalinos is affiliated.

The laboratory has been receiving funding from Nobacco, the market leader in Greek e-cigarettes and the exclusive distributor of British American Tobacco’s nicotine delivery systems since 2018. However, in their published scientific articles, neither Farsalinos nor Poulas had ever declared this Nobacco funding.

Yet the journalists showed that two grants were attributed in 2018 by the Foundation for a Smoke Free World—a non-profit established by tobacco company Philip Morris International in 2017—to ‘Patras Science Park’.

The grants, which according to tax documents came close to €83 000, went to NOSMOKE, a university start-up incubator headed by Poulas, which markets an ‘organic’ vaping product.

Last month, the European Respiratory Journal retracted a paper with Poulas and Farsalinos as co-authors, after two other authors failed to disclose conflicts of interest.

The retracted article had found that “current smoking was not associated with adverse outcome” in patients admitted to hospital with COVID, and it claimed that smokers had a significantly lower risk of acquiring the virus.

The foundation has invested heavily in the COVID/nicotine hypothesis, said Horel and Keyzer.

In June 2020 it set aside €900 000 for research “to better understand the associations between smoking and/or nicotine use, and COVID-19 infection and outcome.”

Its request stated that the pandemic offered “both an opportunity and a challenge for individuals to quit smoking or transition to reduced risk nicotine products.”

They concluded that, in 2021, “amid a global lung disease pandemic, tobacco industry figures are increasingly pushing the narrative of nicotine as the solution to an addiction that they themselves created, with the aim of persuading policy makers to give them ample room to market their “smoke-free” products. This makes studies on the hypothetical virtues of nicotine most welcome indeed.”

Source: Medical Xpress

Article information: Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine, The BMJ, DOI: 10.1136/bmj.n1303 , www.bmj.com/content/373/bmj.n1303

Researchers Discover that Humans can Readily Develop Echolocation Ability

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The ability for humans to sense their surrounding space with reflected sounds might sound like a superhero’s ability, but it is a skill that is developed by some blind people, who use clicks as a form of echolocation.

Echolocation is an ability known in dolphins, whales and bat species, which occurs when such animals emit a sound that reflects off objects in the environment, returning echoes that provide information about the surrounding space.

Existing research has shown that some blind people may use click-based echolocation to judge spaces and improve their navigation skills. Armed with this information, a team of researchers led by Dr Lore Thaler explored how people acquire this skill.

Over the course of a 10-week training programme, the team investigated how blindness and age affect learning of click-based echolocation. They also studied how learning this skill affects the daily lives of people who are blind.

Both blind and sighted people between 21 and 79 years of age participated in this study, which provided a training course of 10 weeks. Blind participants also took part in a 3-month follow up survey assessing how the training affected their daily life.

Both sighted and blind people improved considerably on all measures, and in some cases performed as well as expert echolocators did at the end of training. A surprising result was that a few sighted people even performed better than those who were blind.

However, neither age nor blindness limited participants’ rate of learning or in their ability to apply their echolocation skills to novel, untrained tasks.

Furthermore, in the follow up survey, all participants who were blind reported improved mobility, and 83% reported better independence and wellbeing.

Age or vision not a limitation

Overall, the results suggest that the ability to learn click-based echolocation is not strongly limited by age or level of vision. This has positive implications for the rehabilitation of people with vision loss or in the early stages of progressive vision loss.

Click-based echolocation is not presently taught as part of mobility training and rehabilitation for blind people. There is also the possibility that some people are reluctant to use click-based echolocation due to a perceived stigma around  the click sounds in social environments.

Despite this, the results indicate that both blind people who use echolocation and people new to echolocation are confident to use it in social situations, indicating that the perceived stigma is likely less than believed.

Source: Durham University

Journal information: Human click-based echolocation: Effects of blindness and age, and real-life implications in a 10-week training program, PLOS ONE (2021)

First Detection of Zika Viral DNA in African Bats

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Researchers have, for the first time, detected Zika virus RNA in free-ranging African bats, which indicates that the bats were previously infected with Zika virus at the time the samples were taken. 

This discovery also marks the first time scientists have published a study on the detection of Zika virus RNA in any free-ranging bat.

The findings have ecological implications and raise questions about how bats are exposed to Zika virus in the wild. The study was led by Dr Anna Fagre, a veterinary postdoctoral fellow at Colorado State University’s Center for Vector-Borne Infectious Diseases. The findings were detailed in the journal Scientific Reports.

Dr Fagre said that while other studies have shown that bats are susceptible to Zika virus in controlled experimental settings, detection of nucleic acid in bats in the wild indicates that it was transmitted by bites from infected mosquitoes.

“This provides more information about the ecology of flaviviruses and suggests that there is still a lot left to learn surrounding the host range of flaviviruses, like Zika virus,” she said. Other flaviviruses that cause disease in humans include West Nile and dengue.

Wide-ranging samples

Senior author Rebekah Kading, Assistant Professor at CSU, said she, Dr Fagre and the research team were hoping the project would help them to find out more about potential reservoirs of Zika virus.

With 198 samples from bats gathered in the Zika Forest and surrounding areas in Uganda, the team confirmed Zika virus in four bats representing three species. The samples date back as far as 2009 from different parts of Uganda, which is years before the large Zika outbreaks in 2015 to 2017 in North and South America.

The Zika virus was declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers

“We knew that flaviviruses were circulating in bats, and we had serological evidence for that,” said Prof Kading. “We wondered: Were bats exposed to the virus or could they have some involvement in transmission of Zika virus?”

The virus detected by the team in the bats was most closely related to the Asian lineage Zika virus, the strain that caused the epidemic in the Americas following outbreaks in Micronesia and French Polynesia. The Asian lineage Zika virus was in late 2016 first detected in Africa, in Angola and Cape Verde.

“Our positive samples, which are most closely related to the Asian lineage Zika virus, came from bats sampled from 2009 to 2013,” said Prof Fagre. “This could mean that the Asian lineage strain of the virus has been present on the African continent longer than we originally thought, or it could mean that there was a fair amount of viral evolution and genomic changes that occurred in African lineage Zika virus that we were not previously aware of.”

Likely incidental hosts, not reservoirs

Prof Fagre said that the relatively low prevalence of Zika virus found indicates that bats may only be incidental hosts of Zika virus infection, rather than amplifying hosts or reservoir hosts.

“Given that these results are from a single cross-sectional study, it would be risky and premature to draw any conclusions about the ecology and epidemiology of this pathogen, based on our study,” she said. “Studies like this only tell one part of the story.”

The research team also made an assay for the study which focuses on subgenomic flavivirus RNA, sfRNA, which flaviviruses possess. Testing for Zika normally uses PCR, polymerase chain reaction, to identify bits of genomic RNA, the nucleic acid that results in the production of protein, said Fagre.

The team’s next steps will be to characterise how long these RNA fragments persist in tissues, which will allow them to estimate how long ago these bats were infected with Zika virus, Prof Kadling said.

“There is always a concern about zoonotic viruses,” she said. “The potential for another outbreak is there and it could go quiet for a while. We know that in the Zika forest, where the virus was first found, the virus is in non-human primates. There are still some questions with that as well. I don’t think Zika virus has gone away forever.”

Source: Colorado State University

Journal information: Fagre, A. C., et al. (2021) Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae). Scientific Reports. doi.org/10.1038/s41598-021-87816-5.

Gift of The Givers Rescues Hospital by Drilling for Water

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Three weeks into Johannesburg’s water crisis, which has put tremendous strain on hospitals amid the pandemic, Gift of the Givers have said they will drill for water at Rahima Moosa Mother and Child Hospital.

“Having delivered bottled water on 28 and 31 May, Gift of the Givers drilling teams will be arriving at the hospital shortly, having been granted permission by the management and infrastructure team to drill for water,” said Imtiaz Sooliman, founder of the non-governmental disaster response organisation, the largest African one on the continent.

According to the Daily Maverick, Johannesburg Water’s infrastructure woes are the consequence of years of chronic under-funding. In its business plan for the year, the entity has “has an infrastructure renewal backlog of approximately R19.9-billion as a result of underfunding, which has also led to having 25% of the asset base (reservoirs, towers, pipes, etc) that has a remaining useful life of less than 10 years.”

Amidst concerns about knock-on effects on facilities such as Helen Joseph and Rahima Moosa hospitals, Gauteng health department spokesperson Kwara Kekana said that since last week, the hospitals’ management were trying to ease the pressure on the two worst affected facilities by transferring some patients to other hospitals and performing some theatre operations at sister hospitals.

Hospital staff and management had approached Gift of the Givers, requesting bottled water, portable toilets and any means to augment the water tankers arriving daily.

Rahima Moosa is one of the feeder hospitals for the temporarily closed Charlotte Maxeke Hospital and healthcare workers trying to work through a backlog of non-COVID patients between the second and third waves. It couldn’t have come at a worse time, said Sooliman,

“Add to that a desperate community thronging to the hospital in search of drinking water, clearly worsening COVID risk,” he said.

Sooliman said a drilling site had been identified.

“Existing, defunct boreholes will be assessed with a view to resuscitating them while drilling for new boreholes then pumping water directly into the hospital infrastructure using booster pumps and setting up taps outside the hospital for community use once the water has been tested and approved for human consumption,” said Sooliman.

Bottled water from companies will be welcomed while they waited for the work to be completed, he added.

Source: Times Live