Categories : CancerTags :

Tumour Weakened against Radiation by Tweaking a Certain Protein

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The vulnerability of specific tissues to ionising radiation has been linked to the time-varying levels of a tumour-suppressing protein, opening new avenues for cancer combination therapy.

The ability for cells to survive radiation damage has been known to be connected to p53, but tissues with vastly different levels of p53 have been shown to have great differences in sensitivity. In the face of this apparent paradox, researchers from Blavatnik Institute at Harvard Medical School, Massachusetts General Hospital, and the Novartis Institutes for BioMedical Research investigated the behaviour of p53 in irradiated tissues.

“Dynamics matter. How things change over time matters,” said co-corresponding author Galit Lahav, the Novartis Professor of Systems Biology at HMS. “Our ability to understand biology is limited when we only look at snapshots. By seeing how things evolve temporally, we gain much richer information that can be critical for dissecting diseases and creating new therapies.”

Ionising radiation randomly damages a cell’s molecular machinery, causing it to initiate cell death if it is too serious. The arbitrator of cellular suicide is p53, which is also involved in tumour suppression. 

The findings opened new avenues for combination cancer therapies, as they discovered that administering a drug that blocks p53 levels from oscillating resulted in tumours in mice being more susceptible to radiation. 
Administering to the mice an experimental anti-cancer drug that inhibits MDM2, a protein which degrades p53, they forced p53 to stay elevated. The large intestine, which is normally radiation resistant, showed increased vulnerability.

Testing out this enhanced vulnerability on human tumours transplanted into mice, a significant tumour shrinkage was seen following radiation and then MDM2 inhibitor administration.

Co-corresponding author Galit Lahav, Novartis Professor of Systems Biology, Harvard Medical School explained: “By irradiating first, we force the cancer cells to activate p53, and by adding MDM2 inhibitor on top of that, we can keep p53 active longer. This combination has a much stronger effect than either alone.”

The findings showed the importance of understanding the role of p53 in cancer, the dynamic nature of which is not being looked at in studies testing MDM2. More research into the biological pathways of p53 is called for. 
“For a lab studying p53, cancer is always a major motivation. Our goal is to acquire knowledge to help develop better and more efficient therapies,” Lahav said. “Understanding how p53 behaves over time in different conditions is a critical piece of the puzzle.”

Source: News-Medical.Net

Journal information: Stewart-Ornstein, J., et al. (2021) p53 dynamics vary between tissues and are linked with radiation sensitivity. Nature Communications.doi.org/10.1038/s41467-021-21145-z

Categories : Cancer ImmunologyTags :

Immune Cells in Prostate Tumours Boost Survival with Immunotherapy

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A new Northwestern Medicine study discovered the reason why black men are more likely to survive prostate cancer when given immunotherapy. 

Black men die more often from prostate cancer, yet are more likely to respond to immunotherapy. The increased presence of a type of immune cell in the tumours of black men appears to be related to their increased odds of survival with immunotherapy. The findings will be published on February 10 in Nature Communications.

A research team by Dr Edward Schaeffer, chair of urology at Northwestern University Feinberg School of Medicine and Northwestern Medicine, found that men who survive prostate cancer with immunotherapy have been found to have more plasma cells. Plasma cells are a type of specially differentiated B cell, which secrete antibodies and play a key role in the adaptive immune response.

“If a man’s prostate cancer has numerous plasma cells, we found he had improved cancer survival,” Schaeffer said. “Our study suggests plasma cells are important in the body’s response to cancer.”

Recent studies have shown that black men with advanced prostate cancer have on average better response to immunotherapy than white men. However, there has been no way to determine which individuals would have a better response, regardless of race.

Schaeffer’s team went through the genomics of 1300 tumour samples classified to genetic ancestry or self-identified race, and found more plasma cells in the tumours of black men than those of white men. However, the finding was not unique to black men alone, as elevated plasma cells in all men raised the odds of cancer-free survival after surgery.

“The finding comes at a time as researchers are discovering plasma cells may play a greater role in cancer immunotherapy than previously thought,” said first author Dr. Adam Weiner, a Northwestern Medicine urology resident. “Testing for plasma cells in prostate cancer may help identify men who will benefit from immune-based treatments.”

Source: Medical Xpress

Categories : Medical Research & TechnologyTags :

New Biomaterials Could Boost Vaccines or Self-sterilise PPE

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Researchers from the Indian Institute of Science describe two technologies currently being researched that could be of great benefit in fighting viruses.

These technologies could enhance the effectiveness of vaccines, and also make surfaces destructive to viruses.

“It is important not just in terms of COVID,” explained author Kaushik Chatterjee. “We’ve seen SARS, and MERS, and Ebola, and a lot of other viral infections that have come and gone. COVID has, of course, taken a different turn altogether. Here, we wanted to see how biomaterials could be useful.”

The technologies combine the field of biomaterials, which are designed to interact with biological systems, along with nanotechnology, where structures are engineered on a tiny scale. Biomaterials have been used for dental implants and joint replacements, while nanotechnology has been harnessed for drug delivery systems.

One application the authors describe is the combination of nanotechnology and biomaterial could be used to prepare the immune system to recognise vaccine antigens.

“It is a means of stimulating the immune cells which produce antibodies during the vaccination,” explained author Sushma Kumari. “It is like a helper, like priming the cells. Now, the moment they see the protein, the cells are more responsive to it and would be secreting more antibodies.”

Another technology application is surfaces that disinfect themselves. By putting an electrical charge onto the surfaces, they could be made into a hostile coating that damages or destroys virus particles when they fall onto them. These surfaces could be used for PPEs and high-touch items such as doorknobs. This would save considerable time, effort and expense in regularly disinfecting surfaces with chemicals or UV irradiation. A similar existing technology is the use of silver nanoparticles as antibacterial medical device coatings.

This technology is very much in its early stages, the researchers stressed. Research needs to be done on which biomaterials are suitable for fighting viruses, and the solution for one disease may not be applicable to another.

Source: Medical Xpress

Journal information: “Biomaterials-based formulations and surfaces to combat viral infectious diseases” APL Bioengineering, DOI: 10.1063/5.0029486

Categories : Ageing COVID General InterestTags :

Europe’s Oldest Living Person, 116, Survives COVID

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A 116 year old French nun who is Europe’s oldest living person has survived COVID after testing positive.

French nun Sister Andrée had tested positive for COVID in her retirement home in Toulon, but had remained symptom-free. Most of the 88 residents at the home contracted the virus, 10 of whom died. 

Sister Andrée, who is blind and in a wheelchair, said that her main complaint was the solitude necessitated by being confined to her room.
“I didn’t even realise I had it,” she told Var-Matin newspaper:

David Tavella, a spokesperson for the nursing home, told the newspaper that she had no fear of the virus.

“She didn’t ask me about her health but about her routine. She wanted to know for example if the meal and bed times were going to change. She showed no fear of the illness, in fact she was more worried about the other residents,” Mr Tavella said.

When asked by France’s BFM Television if she had been scared of having COVID, she responded: “No, I wasn’t scared because I wasn’t scared to die … I’m happy to be with you, but I would wish to be somewhere else – join my big brother and my grandfather and my grandmother.”

In addition to being Europest oldest living person, she is also the world’s second oldest living person. The oldest living person in the world is Kane Tanaka in Japan, who turned 118 on January 2. Having lived through the First World War as a child, Sister Andrée will turn 117 on Thursday.

Source: The Guardian

Categories : COVIDTags :

Wrong Syringes in Japan Will Waste Millions of Vaccine Doses

On By ModernMedia

When it begins inoculations, Japan will lose millions of vaccine doses because of a lack of the ‘low dead space’ syringes needed to extract the maximum number doses from each vial.

Japan had ordered 144 million doses of the Pfizer vaccine on the assumption that each vial equated to six doses. Low dead space syringes leave less vaccine in the syringe after injection, especially around the base of the needle, and result in minimal wastage. However, since low dead space syringes are in short supply in that country, regular syringes will have to be used which can only withdraw enough vaccine for five doses. This will result in the wastage of up to 24 million doses of vaccine.

“The syringes used in Japan can only draw five doses,” health minister Norihisa Tamura said, quoted by the Kyodo news agency. “We will use all the syringes we have that can draw six doses, but it will, of course, not be enough as more shots are administered.”

In large-scale vaccination programmes, the wasted vaccine in each vial becomes an issue. Skill is a factor in preserving the vaccine, but the amount of dead space in a syringe and the achievable accuracy also has a significant effect. One study showed that the amount that can be withdrawn from each vial can vary by as much 42% depending on the type of syringe used.
The US and EU have also reported shortages of low dead space syringes, and this may result in competition and supply shortages.

Japan is set to begin the first round of inoculations with 10 000 to 20 000 healthcare workers, and from there giving priority to other healthcare workers and vulnerable individuals. Inoculations for those aged 16 to 59 are not expected to begin until July.

Source: The Guardian

Categories : PaediatricsTags :

Caffeine Shown to Alter Brain Pathways in Utero

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Caffeine consumption during pregnancy could change key brain pathways, resulting in children having significant behavioural problems in later life. 

“These are sort of small effects and it’s not causing horrendous psychiatric conditions, but it is causing minimal but noticeable behavioural issues that should make us consider long term effects of caffeine intake during pregnancy,” said John Foxe, PhD, director of the Del Monte Institute for Neuroscience. “I suppose the outcome of this study will be a recommendation that any caffeine during pregnancy is probably not such a good idea.” Foxe also pointed out that this was a retrospective study, reliant on mothers’ recall of caffeine consumption.

Studies had already linked caffeine to other outcomes, such as a meta-review which found a nearly linear link between caffeine consumption and low birth weight. It is known that foetuses do not possess the enzyme necessary to break down caffeine, which crosses the placenta into the foetal bloodstream.

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) analysed brain scans of thousands of children. The researchers observed increased behavioural and attention problems along with hyperactivity in these children. They observed distinct changes in how the white matter tracks (which connect brain regions) were organised in children of mothers who reported caffeine consumption during pregnancy.

“What makes this unique is that we have a biological pathway that looks different when you consume caffeine through pregnancy,” said first author Zachary Christensen, an MD/PhD candidate in the Medical Science Training Program. “Previous studies have shown that children perform differently on IQ tests, or they have different psychopathology, but that could also be related to demographics, so it’s hard to parse that out until you have something like a biomarker. This gives us a place to start future research to try to learn exactly when the change is occurring in the brain.”

At this stage it is not known what the relationship between amounts of caffeine are, or what effects arise in each trimester.

“Current clinical guidelines already suggest limiting caffeine intake during pregnancy—no more than two normal cups of coffee a day,” added Christensen. “In the long term, we hope to develop better guidance for mothers, but in the meantime, they should ask their doctor as concerns arise.”

Source: Medical Xpress

Journal information: Zachary P. Christensen et al, Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9–10 year old children, Neuropharmacology (2021). DOI: 10.1016/j.neuropharm.2021.108479

Categories : Diseases, Syndromes and ConditionsTags :

Treating Periodontitis can Reduce Risks of Certain Other Diseases

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A steadily growing body of evidence points to a two-way connection between oral health and systemic disease.

Periodontitis, the inflammation and disease of tissues surrounding the teeth, is already known to be a result of type 2 diabetes, but there is research to suggest that it may also cause diabetes—as well as certain other diseases.

“What happens in your body impacts your mouth, and that in turn impacts your body. It’s truly a cycle of life,” said Professor Purnima Kumar of The Ohio State University. “What is more dynamic than the gateway to your body – the mouth?” she continued. “It’s so ignored when you think about it, and it’s the most forward-facing part of your body that interfaces with the environment, and it’s connected to this entire tubing system. And yet we study everything but the mouth.”

The link between oral health and type 2 diabetes was first established in the 1990s, and Prof Kumar has led many investigations into this area. She was lead author in a study published last year that investigated the oral microbiomes of people with and without type 2 diabetes, and the effects of nonsurgical periodontitis treatment.

“Our studies have led up to the conclusion that people with diabetes have a different microbiome from people who are not diabetic,” Prof Kumar said. “We know that changing the bacteria in your mouth and restoring them back to what your body knows as healthy and friendly bacteria actually improves your glycemic control.”

The rough picture that has emerged is that oral bacteria are aerobic, but even small changes such as a few days of not brushing teeth can trigger a cascade that results in the bacteria shifting to an anaerobic, fermentative state producing toxins and byproducts. It becomes, as Prof Kumar puts it, “a septic tank” that stimulates the immune system and causes an inflammatory state, producing signalling products that bacteria then feed on.

“Then this community – it’s an ecosystem – shifts. Organisms that can break down protein start growing more, and organisms that can breathe in an oxygen-starved environment grow. The bacterial profile and, more importantly, the function of the immune system changes,” she explained.

The inflammation causes pores to open in the lining of the mouth, allowing the bacteria entry to the body.

“The body is producing inflammation in response to these bacteria, and those inflammatory products are also moving to the bloodstream, so now you’re getting hammered twice. Your body is trying to protect you and turning against itself,” Prof Kumar said. “And these pathogens are having a field day, crossing boundaries they were never supposed to cross.”

Though the relationship between oral health and certain disease is a complex one, Prof Kumar said prevention was exceedingly simple. Daily brushing and flossing with twice-yearly dentist visits for cleaning were sufficient.

Source: News-Medical.Net

Journal information: Kumar, P. S., et al. (2020) Subgingival Host-Microbial Interactions in Hyperglycemic Individuals. Journal of Dental Research. doi.org/10.1177/0022034520906842. 

Categories : Ageing General Interest Neurodegenerative DiseasesTags :

Legendary Singer Tony Bennett Diagnosed with Alzheimer’s

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Music legend Tony Bennett, 94, revealed in an interview that he was diagnosed with Alzheimer’s disease 4 years ago.

The singer’s career has spanned seven decades, he had continued his initial success in the 1950s across multiple genres, becoming a hit with the MTv generation, and in more recent years collaborating with popular artists like Amy Winehouse and Lady Gaga.

Alzheimer’s disease is an age-related, irreversible neurodegenerative condition. In more than 90% of patients, it begins after age 65, although it can occur as early as in the 30s. It is marked by memory loss and confusion that seem like the normal cognitive decline of older age, but it is more rapid and severe, eventually resulting in death. As people live longer and the risks of developing this disease increase with age, the burden of this disease is expected to increase in the future. In the US, the number of people with Alzheimer’s is expected to nearly triple from 5.5 million to 14 million by 2060.

Mr Bennett has been able to work over the past four years but the toll is perceptible. He still recognises his family members but his short-term and long-term memory have drastically deteriorated. Interviewer John Colapinto noted Mr Bennett gazing at his lavishly illustrated book, “Tony Bennett Onstage and in the Studio” (2018). “He stared into its pages not with the air of warm reminiscence but like a man struggling to recall why these images seemed familiar.” His wife, Susan, added that Mr Bennett is “not always sure where he is or what is happening around him. Mundane objects as familiar as a fork or a set of house keys can be utterly mysterious to him.”

Over the past two years, Mr Bennett recorded a second album of duets with Lady Gaga, a follow-up to the hit album with Gaga in 2014. While he had been known to be a “meticulous and hard-driving perfectionist in the studio,” Mr Bennett was much more subdued. speaking rarely, his words coming haltingly and seeming lost or bewildered. Gaga, who considers Mr Bennett to be “an incredible mentor, and friend, and father figure” is seen breaking down in tears as Tony sings a solo passage of a love song.

The album is due to be released this spring, but Mr Bennett will be unable to do promotional interviews. Mr Bennett, together with his wife and son (who is also his manager) decided to break the news, in the hopes that as many fans as possible know about what will likely be his final record. The neurologist who diagnosed Bennett in 2016,  Gayatri Devi, MD, said: “He is doing so many things, at 94, that many people without dementia cannot do. He really is the symbol of hope for someone with a cognitive disorder.”

Source: MedPage Today

Categories : COVIDTags :

SARS-CoV-2 Mutation Evolved in Immunocompromised Patient

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The discovery of SARS-CoV-2 mutations evolving in an immunocompromised patient treated with convalescent plasma has been revealed by Ravindra Gupta, MD, PhD, of University of Cambridge in England, and team.

“We have documented a repeated evolutionary response by SARS-CoV-2 in the presence of antibody therapy during the course of a persistent infection in an immunocompromised host,” the authors wrote.

Previous research has shown that immunosuppressed patients could serve as reservoirs for norovirus variants.

Although they did not claim the UK variant was created by that particular case, Gupta’s group speculated that the plasma therapy could have unleashed the resistant variants, and could do so in other immunosuppressed patients too.

They wrote that, in such patients, “the antibodies administered [in plasma] have little support from cytotoxic T cells, thereby reducing chances of clearance and theoretically raising the potential for escape mutations.” 

They cautioned that convalescent plasma use should be limited, and only with appropriate infection control in monitoring in immunosuppressed patients.

A man in his 70s, who had received immunotoxic chemotherapy to treat lymphoma eight years previously, was initially hospitalised in May with neutropenic sepsis, and, about a week later, tested positive for SARS-CoV-2. He was discharged later in May, but in late June was readmitted with cough and breathlessness.

His condition worsened and he received dexamethasone and two 10-day courses of remdesivir 5 days apart. On two days around July 20, convalescent plasma was administered; more remdesivir and convalescent plasma was administered about 4 weeks later. He died shortly afterward.

Gupta and team took viral samples from this patient on 23 occasions, and over the first 57 days, they observed little change in viral population upon treatment with remdesivir, but after the July round of convalescent plasma, a shift in viral genotype occurred.

Initially the patient’s viral serotype showed a mutation first reported in China. However, in late July, a variant was observed with two alterations in the spike protein, including the deletion seen in the B.1.1.7 variant. Testing showed a twofold reduced susceptibility to the antibodies in the convalescent plasma.

The team wrote that this sort of evolution is unlikely to emerge in immunocompetent patients. They cautioned against using convalescent plasma in severe COVID patients, and especially those who were immunosuppressed.

The study’s limitations included being only a single case, and samples were taken from the upper respiratory tract and not the lower respiratory tract. 
Given South Africa’s large HIV positive population, if viral evolution is driven by convalescent plasma in immunosuppressed patients, this raises questions for the country’s COVID strategy.

Source: MedPage Today

Journal information: Kemp SA, et al “SARS-CoV-2 evolution during treatment of chronic infection” Nature 2021; DOI: 10.1038/s41586-021-03291-y.

Categories : COVIDTags :

As COVID Variants Dominate, Better Mask Use is Needed

On By ModernMedia

Evidence is accumulating that COVID is commonly transmitted through small aerosolised droplets emitted during regular speaking and breathing—a problem compounded by the enhanced contagiousness of variants such as 501Y.V2, the strain which dominates in South Africa.

Masks have become ubiquitous in the pandemic-struck world, and even fashionable, with many different types available. However, their effectiveness varies considerably from top-of-the-range N95 masks to a pulled-up shirt which offers very little protection.
“How well a mask works depends on two things: filtration and fit,” said Professor Linsey Marr, who studies airborne disease transmission at Virginia Tech .

“Good filtration removes as many particles as possible, and a good fit means that there are no leaks around the sides of your mask, where air—and viruses—can leak through,” she said, noting that even a small gap could result in a 50% reduction in effectiveness.

We do not recommend wearing more than two masks. Adding more layers proves diminishing returns and can compromise breathability. It must remain easy to breathe through the layers; otherwise, air is more likely to leak in around the sides of the mask.

Wearing a cloth mask over a surgical mask, or ‘double masking’ does improve effectiveness as it serves to tighten the surgical mask’s fit. Air escapes around the corners and edges of the mask, as anyone who has worn glasses and had them fog up in the cold can attest to.

While N95 masks are the best available, there are also equivalents such as KN95 or FFP2.

“They all provide a similar level of filtration, meaning protection of particles going in and out,” said Ranu Dhillon, a global health physician at Brigham and Women’s Hospital and Harvard Medical School. Dhillon is frustrated at the lack of transparency and education for the public about masks.

Health care workers, for example, get their masks tested for fit, something which could be also done by members of the public.

Donald Milton, a professor of environmental health at the University of Maryland, said that the key to understanding the COVID airborne transmission threat is to treat it like cigarette smoke. Ventilation helps, but if you have someone between you and an exhaust vent, then masks will definitely help.

Before the pandemic, Milton and Dhillon courted controversy by demonstrating that most viral transmission was in the form of small droplets emitted when speaking or breathing, and the contribution to transmission by coughing and sneezing was smaller than previously thought. The two researchers are hopeful that their findings will find their way into official COVID policy, and future research may even see masks becoming a common sight during peak flu seasons.

Source: Japan Times