Year: 2021

Categories : COVIDTags :

Volunteers to Take Part in COVID Human Challenge Trial

On By ModernMedia

The first trial of its kind is set to start in the UK, with healthy volunteers being sought to be deliberately infected with COVID in a human challenge test.

The study will seek 90 healthy volunteers aged 18-30 to be infected with COVID in a safe, controlled environment. Among the study’s objectives is a desire to find out exactly how much of a viral load is needed to infect someone with COVID.

The window of opportunity in the UK for a large-scale study of this type is gradually closing because eventually it will no longer be possible to find people have not been vaccinated. However, a significant amount of information can be gleaned from even small-scale studies. This includes how second-generation vaccines compare to how well vaccines protect against new variants.

Human challenge tests have been an important part of developing understanding of and treatments for a number of diseases. The first human challenge trials for dengue fever took place in the 1900s. Although abandoned in favour of animal testing, animals were not sufficiently close to humans to advance research. Recent human challenge trials helped to develop an effective vaccine for the disease.

Clive Dix, interim chair of the Vaccines Taskforce, explained: “We have secured a number of safe and effective vaccines for the UK, but it is essential that we continue to develop new vaccines and treatments for Covid-19.

“We expect these studies to offer unique insights into how the virus works and help us understand which promising vaccines offer the best chance of preventing the infection.”

Applicants will be screened, including determining if they had COVID before, and then be intranasally infected with the virus. Volunteers will receive compensation of £4500 (about R90 000) over the course of a year, which will include follow-up tests.

Source: BBC News

Categories : Cancer Medical Research & TechnologyTags :

Neural Network Matches Dermatologists’ Assessment of Skin Lesions

On By ModernMedia

Researchers have developed an AI-based tool that can use smartphone camera pictures to spot suspicious pigmented lesions (SPLs) with an accuracy close to that of professional dermatologists.

Such technology would hardly put dermatologists out of work; on the contrary, there is a great need for readily available skin cancer screening. In the US, there are only 12 000 practising dermatologists, who would need to see over 27 000 patients each per year in order to screen the entire population for SPLs which could lead to cancer. Computer-aided diagnosis (CAD) has thus been developed over previous years to help assist in diagnosis, but thus far had failed to spot melanomas in a meaningful way. Such CAD programs only analyse individual SPLs, while dermatologists compare other lesions on the same patient to reach a diagnosis, called ‘ugly duckling’ criteria.

This shortcoming has been addressed in a new CAD system that uses convolutional deep neural networks (CDNNs) developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Massachusetts Institute of Technology (MIT).

The new system was able to distinguish SPLs from non-suspicious lesions in photos of patients’ skin at ~90% accuracy, and established an ‘ugly duckling’ criteria which could match three dermatologists’ consensus 88% of the time.

“We essentially provide a well-defined mathematical proxy for the deep intuition a dermatologist relies on when determining whether a skin lesion is suspicious enough to warrant closer examination,” said first author Luis Soenksen, PhD, a Postdoctoral Fellow at the Wyss Institute who is also a Venture Builder at MIT. “This innovation allows photos of patients’ skin to be quickly analyzed to identify lesions that should be evaluated by a dermatologist, allowing effective screening for melanoma at the population level.”

The researchers used a database of 33 000 images to train the system, which also included background elements and non-skin elements. These extraneous elements were left in so that the CDNN would be able to use normal images taken by consumer-grade cameras. The images contained SPLs and non-suspicious skin lesions identified by three certified dermatologists.
The software then developed a ‘map’ of how far away a lesion was from the others in terms of similarity, giving an ‘ugly duckling’ criteria. To test the software, they used 135 photos from 68 patients, which assigned an ‘oddness’ score to each lesion. This was then compared to dermatologists’ assessments of those lesions, matching individual dermatologists 88% of the time and their consensus 86% of the time
“This high level of consensus between artificial intelligence and human clinicians is an important advance in this field, because dermatologists’ agreement with each other is typically very high, around 90%,” said co-author Jim Collins, PhD, of the Wyss Institute, who is also the Termeer Professor of Medical Engineering and Science at MIT. “Essentially, we’ve been able to achieve dermatologist-level accuracy in diagnosing potential skin cancer lesions from images that can be taken by anybody with a smartphone, which opens up huge potential for finding and treating melanoma earlier.”

Source: Medical Xpress

Journal information: “Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images” Science Translational Medicine, 2021.

Categories : Diet and Nutrition General InterestTags :

Health Experts Call for a Sugar Tax Increase to 20%

On By ModernMedia

In advance of Finance Minister Tito Mboweni’s annual budget presentation on 24 February, health specialists have been calling for an increase in the health promotion levy from 11% to 20%. 

The health promotion levy (or ‘sugar tax’) was put into effect in April 2018, and imposes an 11% tax on sugar sweetened beverages. Specialists called for an increase in this tax on Tuesday at a webinar rub by the Healthy Living Alliance (Heala), saying that this was a prudent time to do it because the health sector is currently battling the COVID pandemic.

Most people hospitalised with COVID in SA have comorbidities such as diabetes and hypertension, said Karen Hofman, director of the Wits Centre for Health Economics and Decision Science (Priceless SA). Sugar, especially in liquid form, is a risk factor for obesity, diabetes, hypertension, cardiovascular disease, a number of common cancers and dental decay. She added that had those comorbidities had been prevented, the country could have been in a much better position.

Hofman said that people think they have “control over what [they] are eating and drinking”, but in fact don’t, having been heavily influenced by their environment from an early age. For the tax to have any effect, it should be increased to 20%, based on the World Health Organization and other health experts’ recommendations.

Heala head, Lawrence Mbalati, said the sugar tax had created R5.4-billion for the government within its first two years. This would have been enough to finance South Africa’s downpayment for COVID vaccines from the Covax facility almost 20 times over, in spite of its minimal contribution to the overall budget. 

A doubling of the sugar tax would net an additional R2 billion to help fight COVID, Mbalati said.

“This is a watershed moment for the country,” Mbalati continued. “Government revenues are under immense pressure and funding the fight against Covid-19, including vaccines, remains critical.”

Hofman said that research in other countries with a sugar tax had shown a fall in volume of taxable beverages by 51%, and a 29% reduction in sugar intake.

“SA must address commercially driven epidemics with taxes, mandatory food labelling and mandatory comprehensive marketing bans,” Hofman said.

Source: Mail & Guardian

Categories : CancerTags :

Osmium in Cancer Cells May Be a Useful Weapon

On By ModernMedia

Using powerful X-ray beams to probe inside a cancer cell, researchers have determined that osmium could be a viable element for new cancer drugs.

About half of all chemotherapy drugs use platinum, but this has platinum which reacts in the nucleus, possibly leading to undesirable side effects. Osmium is a rare metal which could replace platinum in chemotherapy drugs, but first researchers needed to know where the osmium would wind up. To determine this, the researchers used the Diamond synchrotron to precisely track osmium in human lung cancer cells with a precision of 100 nanometres.

The researchers revealed the functioning of osmium in the cells using synchrotron X-ray Fluorescence (XRF) imaging. This enabled the researchers to observe the osmium in a single lung cancer cell. However, since osmium’s reactivity is determined by its ligand coating, these were labelled with bromine.

Once in the cell, the researchers observed that the osmium stayed in the cytoplasm, while the ligands penetrated into the nucleus, suggesting a twin attack on the cell.

Professor Peter Sadler, from the Department of Chemistry at the University of Warwick explained the use of osmium and their research process: “Osmium is a rare precious metal, however, since it can act as a catalyst, a very little amount is needed for reactions in the cancer cell, therefore it could be a sustainable treatment going forward. We wanted to see how exactly it worked in a single cancer cell, which involved a variety of novel techniques, including taking water molecules out of the cell and rapidly flash-freezing it. Whereas usually cells are chemically altered to see the reactions, in our method they are close to their natural state, making our results more authentic.”

It was hard work, as Dr Elizabeth Bolitho, from the Department of Chemistry and Diamond explained: “We worked 24 hours a day, 5 days a week to collect these exciting data, allowing us to see inside cancer cells to a nanoscale resolution. This has provided crucial insights into potential cellular targets of such Osmium catalysts.

“Not only were we able to track the osmium in a lung cancer cell, but more widely in breast cancer, ovarian and prostate cancer cells, for example, which provides hope that in the future osmium could be used to treat a range of different cancer.”

Source: News-Medical.Net

Journal information: Bolitho, E. M., et al. (2021) Tracking Reactions of Asymmetric Organo‐Osmium Transfer Hydrogenation Catalysts in Cancer Cells. Angewandte Chemie. doi.org/10.1002/anie.202016456.

Categories : COVID Immune SystemTags :

COVID Antibody Drugs Work Best with Immune Cells

On By ModernMedia

Research into the current antibody-based drugs for COVID treatment shows that they need to be designed to work in concert with immune cells to be effective.

Three drugs using monoclonal antibodies are approved by the FDA to treat COVID, which provide the patient’s body with ready-made antibodies faster than can be produced by their own immune systems.

The distinctive Y shape of antibodies comes from their two short arms, which latch on to foreign molecules to clear them out, and a long effector arm which interacts with immune cells, inducing them to attack infected cells and release molecules that modulate the immune response.

In antibody-dependent enhancement, the long arm of antibodies can interfere with immune cells, such as in tropical dengue fever. Immunity against one strain against dengue fever causes life-threatening illness if infected with the other strain.

To investigate the possibility of this in COVID, some companies altered the long arm of their antibodies to prevent interaction with immune cells. Other companies took the opposite approach and strengthened antibody effector functions to boost the potency of their drugs.

“Some of the companies removed the effector functions from their antibodies, and other companies are trying to optimise the effector functions,” said senior author Michael S Diamond, MD, PhD, the Herbert S Gasser Professor of Medicine. “Neither of these strategies is backed by data in the context of SARS-CoV-2 infections. Based on our findings, if you have a potently neutralising antibody without effector functions and you give it before infection, as a preventive, it will probably work. But if you give it after infection, it won’t work well; you need to optimise effector functions to get maximal benefit.”

“‘Effector functions’ refers to a complex set of interactions between antibodies and other elements of the immune system,” said Prof Diamond, who also is a professor of molecular microbiology and of pathology and immunology. “You can introduce different point mutations to augment certain kinds of effector functions, and some might be harmful to the immune response while others might be beneficial. There’s a lot of nuance. We are still learning how to harness effector functions so you get what you want but not what you don’t want.”

To find how antibody effectors work with COVID, the researchers took an antibody which was known to be effective against the virus and disabled the effector so it could not interact with immune cells.

They administered the original antibodies, the disabled antibodies and placebo antibodies each to a different group of mice, which were infected a day later with SARS-CoV-2. Both normal and disabled effector antibodies were able to protect against the disease. There were no signs of antibody enhancement of the disease, fortunately.

To find out whether the effector function was needed for treatment after infection, they infected mice with SARS-CoV-2 and administered one of the three sets of antibodies to mice  one, two or three days later. Only the original antibodies protected the mice from the disease. The tests were run in hamsters with the same results.

The researchers discovered in the study that losing effector functions changed the types of immune cells recruited to fight the COVID infection and the way they behaved.

Source: Medical Xpress

Journal information: Emma S. Winkler et al, Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection, Cell (2021). DOI: 10.1016/j.cell.2021.02.026

Categories : COVID Medical IndustryTags :

Over Half of SA Has Had COVID, Says Discovery CEO

On By ModernMedia

From the number of excess deaths in South Africa, it appears that over half of South Africa has been infected with COVID at least once.

The CEO and founder of the Discovery Group, Adrian Gore, has said in an interview on 702’s The Money Show that he believes over half of the South African population has had COVID. He believes that there is “absolutely no ambiguity” that the “sky high” excess death rates recorded in SA are attributable to COVID. He said that the excess deaths point to over 50% of the SA population having been infected with COVID so far.

The latest data released by the South African Medical Research Council (SAMRC) puts the number of excess deaths in SA over the course of the pandemic at 137 731 – nearly triple the official death toll from COVID. Nearly 5000 Discovery members and 12 staff members have died. 
Last week, SA National Blood Service released a study showing that 32% of people in the Northern Cape up to 63% of people in the Eastern Cape had contracted COVID. Gore said that this high infection rate would hopefully reduce the impact of the third wave predicted to arrive in the colder winter months.

“We are hoping that a third wave may take longer and might be less because we think the infection rate has been high.” He said, adding that if the first and second phases of vaccination targetting healthcare workers and vulnerable individuals was completed by mid-year, a third wave might be completely avoided.

He said that young, healthy people who can afford a vaccine should not be able to get one before those who were older and more vulnerable. “Not following this process would mean low-risk people get vaccinated before the clinically vulnerable, resulting in unnecessary illness and death. This cannot and should not happen,” he said in a Linkedin post.

He also refuted the rumour that Discovery was not paying contributions towards non-members’ vaccinations. In fact, he said on The Money Show, that medical aid schemes have extra cash to pay for this since members had been going for fewer treatments during the pandemic. This amounts to some R24 billion in surplus, as revealed by regulatory filings, which would be right in the middle of cost estimates for SA’s entire vaccination programme as opposed to the 30% amount that medical aid companies were being expected to contribute.

Source: Business Insider

Categories : Ageing Cardiovascular Disease Substance UseTags :

Recreational Substances Including Cannabis Linked to Heart Disease

On By ModernMedia

Alcohol, tobacco and cannabis are among recreational drugs that contribute to early-onset atherosclerotic cardiovascular disease (ASCVD) in young people, a study has found.

The study drew on data of more than a million people receiving primary care services throughout the VA Healthcare System in 2014 or 2015, of whom there were 135 703 with premature ASCVD.

A number of independent predictors for first-event ASCVD for men (from age 55) and women (from 65) were picked up. Tobacco (adjusted odds ratio [OR] 1.97) and alcohol use (OR 1.50)  conferred significant additional risk, but the greatest risk increase of generally legal substances was cannabis use (OR 2.65). Cocaine use (OR 2.44), amphetamine use (OR 2.74) and other drug use (OR 2.53) all had very high risk increases.

Those using four or more substances had the greatest risk at nearly nine times normal. Women also had much stronger effect sizes for premature ASCVD than men.

In an accompanying editorial Anthony Wayne Orr, PhD, and colleagues at LSU Health Shreveport, wrote: “Substance use disorders have been associated with an acceleration of the ageing process. We are only young once, and we should do everything in our power to maintain that state as long as we can.”

The editorialists suggested a nationwide ASCVD education campaign targeting people with substance use disorders.

“In addition, clinicians and primary care providers should begin screening their adult and young adult patients with a history of a substance use disorder for symptoms of premature or extremely premature ASCVDs at earlier stages in their patients’ lives,” suggested the editorialists.

Limitations included it being an observational study, lack of socioeconomic data and the cohort being mostly white males, as well as not being able to discern between prescription and recreational amphetamine use.
“Retrospective studies are limited by the available data. While this study supports the association between substance use disorder and early-onset ASCVD, the effect of substance use frequency, dose, and duration cannot be reliably ascertained in this patient sample,” the editorialists stated.

The editorialists recommended that specific biomarkers for substance use-associated cardiovascular disease be identified, and therapeutic window characterised to limit these chronic effects of substance use disorder.

Source: MedPage Today

Journal information: Mahtta D, et al “Recreational substance use among patients with premature atherosclerotic cardiovascular disease” Heart 2021; DOI: 10.1136/heartjnl-2020-318119.

Editorial information: Scott ML, et al “Young at heart? Drugs of abuse cause early-onset cardiovascular disease in the young” Heart 2021; DOI: 10.1136/heartjnl-2020-318856.

Categories : Injury & Trauma Neurology Pain ManagementTags :

New Surgery Improves Prosthetic Use and Reduces Pain

On By ModernMedia

A new type of surgery that links muscles together may improve the precision of prosthetic use and also relieve pain.

In typical amputations, the muscle pairs (such as triceps and biceps) that work together to control the joints are severed. However, an MIT team has discovered that reconnecting these muscles that are in an agonistic-antagonistic (‘push-pull’) relationship improves the sensory feedback and thus precision of the affected limb.

“When one muscle contracts, the other one doesn’t have its antagonist activity, so the brain gets confusing signals,” explained Srinivasan, a former member of the Biomechatronics group now working at MIT’s Koch Institute for Integrative Cancer Research. “Even with state-of-the-art prostheses, people are constantly visually following the prosthesis to try to calibrate their brains to where the device is moving.”

The 15 patients who received the AMI surgery were able to flex their prosthetic ankle joint with more precision than those without it, who were only able to fully extend or flex their joint.

“Through surgical and regenerative techniques that restore natural agonist-antagonist muscle movements, our study shows that persons with an AMI amputation experience a greater phantom joint range of motion, a reduced level of pain, and an increased fidelity of prosthetic limb controllability,” says Hugh Herr, a professor of media arts and sciences, head of the Biomechatronics group in the Media Lab, and the senior author of the paper.

The surgery also had a completely unexpected benefit: the reduction of pain in the amputated area, which can be from neuromas or phantom limb pain. Phantom limb pain can occur in 80% of amputess. Six of the 15 AMI patients reported zero pain. This may be significant as in the five centuries since phantom limb pain was first described, there has not been much advancement in the understanding of it.

“Our study wasn’t specifically designed to achieve this, but it was a sentiment our subjects expressed over and over again. They had a much greater sensation of what their foot actually felt like and how it was moving in space,” Srinivasan says. “It became increasingly apparent that restoring the muscles to their normal physiology had benefits not only for prosthetic control, but also for their day-to-day mental well-being.”

To treat patients who had received the traditional amputation surgery, the team is also working on using muscle grafts to create a ‘regenerative AMI’ procedure that restores the effect of agonist and antagonist muscles.

Source: Medical Xpress

Journal information: Shriya S. Srinivasan el al., “Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2019555118

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Excessive False Positives from SNP Testing in Very Rare Diseases

On By ModernMedia

A widely-used genetic testing technology has a very high rate of false positives for extremely rare genetic diseases, a study has found.

Single nucleotide polymorphism (SNP) chips are DNA microarrays which test genetic variation at hundreds of thousands of specific genome locations. They were initially developed to study common genetic variations, and are excellent tools for tracing ancestry and aso detecting predisposition to common multifactorial diseases such as type 2 diabetes.

Prompted by accounts of women scheduling surgery because of wrongly being informed they had variations in the BRCA1 gene that could lead to very high risks of breast disease, a team from the University of Exeter set out to test the technology. Using data from 50 000 individuals, they found that the majority of rare disease detections were false.

“SNP chips are fantastic at detecting common genetic variants, yet we have to recognise that tests that perform well in one scenario are not necessarily applicable to others,” said senior author Caroline Wright, Professor in Genomic Medicine at the University of Exeter Medical School. “We’ve confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted.”

The team compared data from the SNP chips to data from the UK Biobank which was sequenced with better technology, plus 21 volunteers sharing their consumer genetic data.

They found a false positive rate of 84% for variants that were 1 in 100 000. From the consumer data, 20 of the 21 had at least one false positive for a disease-causing variation.

Co-author Dr Leigh Jackson, Lecturer in Genomic Medicine at the University of Exeter, said the number of such false positives on SNP chips was “shockingly high.”

“To be clear: a very rare, disease-causing variant detected using a SNP chip is more likely to be wrong than right,” said Dr Jackson. “Although some consumer genomics companies perform sequencing to validate important results before releasing them to consumers, most consumers also download their ‘raw’ SNP chip data for secondary analysis, and this raw data still contain these incorrect results. The implications of our findings are very simple: SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient’s medical care, unless they have been validated.”

Source: Medical Xpress

Journal information: BMJ (2021). www.bmj.com/content/372/bmj.n214

Categories : COVIDTags :

Real-world Results for Pfizer Vaccine Match Trials

On By ModernMedia

Encouraging results have been reported from Israel, where the real-world efficacy of the Pfizer vaccine closely matches that seen in clinical trials.

Israel has engaged in the world’s most aggressive COVID immunisation schedule, with some 30% of its population vaccinated by late January with at least one dose.

Israeli health fund Clalit matched 600 000 vaccinated individuals to an equal number of unvaccinated individuals. Those who were vaccinated experienced a similar rate of positive COVID tests as was observed in clinical trial data, equating to a 94% effectiveness. Crucially, almost no severe cases of COVID were observed in vaccinated individuals. This pattern was also seen in the over-70s age group, which is generally underrepresented in trials.

Public health doctor Prof Hagai Levine said that high vaccination coverage of the most susceptible groups was key. However, he said that he could not give an answer as to what number needed to be vaccinated before containment measures could be eased. 

“We still don’t know what the impact is on transmission,” he said. But he added that “the vaccine is useful for personal protection”.

The greatest drop in cases was seen in the over 60s age group, and in areas which had been vaccinated, indicating that this was not the result of lockdown. However, many people still remain unvaccinated, resulting in tens of thousands of cases. Prof Segal noted that the fall in cases was not as rapid as had been hoped, due to the B.1.1.7 or UK strain becoming dominant in Israel.

“We still have to exit our lockdown very cautiously,” he warned, or else hospitalisations would spike again.

The fact that the same rate was observed in clinical trials is important news for other countries, which are watching to see the effects of Israel’s vaccination programme.

Source: BBC News