Categories : Cardiovascular Disease NeurologyTags :

Statins not Associated With Cognitive Decline

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A new study has found that statin use in adults 65 years old or older is not associated with incident dementia, mild cognitive impairment (MCI) or decline in individual cognition domains.

Major health concerns in the elderly, cognitive decline and dementia affect about 10% of people over 60 years old. Statins are used to reduce low-density lipoprotein cholesterol, and are a fundamental treatment for prevention of primary and secondary cardiovascular disease (CVD) events. 
In 2012 the Food and Drug Administration issued a warning about cases of apparent short-term cognitive impairment with statin use, while acknowledging that the cardiovascular benefits outweigh their risks. Systematic reviews have since shown insufficient evidence on the impact of statins, and research has shown mixed results, with some showing a neurocognitive benefit of statins and others reporting a null effect.

“With statins being increasingly prescribed to older adults, their potential long-term effects on cognitive decline and dementia risk have attracted growing interest,” said lead author Zhen Zhou, PhD, Menzies Institute for Medical Research at the University of Tasmania. “The present study adds to previous research by suggesting that statin use at baseline was not associated with subsequent dementia incidence and long-term cognitive decline in older adults.”

Researchers of this study analysed data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. ASPREE was a large prospective, randomized placebo-controlled trial of daily low-dose aspirin with adults 65 or older. One of the key selection criteria of ASPREE was that participants had to have a score of 78 for the Modified Mini-Mental State Examination test, a screening test for cognitive abilities, at enrollment.

The study had 18 846 participants, grouped by their baseline statin use (31.3% of participants) versus non-statin use. The study aimed to measure outcomes including incident dementia and its subclassifications (probable Alzheimer’s disease [AD], mixed presentations); MCI and its subclassifications (MCI consistent with AD, MCI-other); changes in domain-specific cognition including global cognition, memory, language and executive function, and psychomotor speed; and in the composite of these domains.

After a median of 4.7 years of follow-up, researchers found 566 incident cases of dementia (including probable AD and mixed presentations). Compared with no statin use, statin use was not associated with risk of all-cause dementia, probable AD or mixed presentations of dementia. There were 380 incident cases of MCI found (including MCI consistent with AD and MCI-other). Compared to no statin use, statin use was not associated with risk of MCI, MCI consistent with AD or other MCI. No statistically significant difference in the change of composite cognition and any individual cognitive domains between statin users versus non-statin users was seen. However, researchers did find interaction effects between baseline cognitive ability and statin therapy for all dementia outcomes.

The researchers acknowledged several limitations, including observational study bias and lack of data on the length of prior use of statins; and the dose of statins was not recorded in the ASPREE trial, so their effects could not be fully explored. Researchers conclude the study must be interpreted with caution and will require confirmation by randomized clinical trials designed to explore the neurocognitive effects of statins in older populations.

In an accompanying editorial comment, Christie M. Ballantyne, MD, professor at Baylor College of Medicine in Houston, noted study limitations that the authors address, but agreed the findings suggest statins do not contribute to cognitive decline.

“Overall, the analysis was well done, and its main strengths are a large cohort with a battery of standardised tests that allowed the investigators to track both cognition and incidence of dementia and its subtypes over time,” Ballantyne said. “Lingering questions such as the one raised by this analysis regarding potential adverse effects of statins in individuals with mildly impaired cognition can only be answered in randomised controlled trials in the appropriate age group and population and with appropriate testing and adequate follow-up. In the meantime, practising clinicians can have confidence and share with their patients that short-term lipid lowering therapy in older individuals, including with statins, is unlikely to have a major impact on cognition.”

Source: American College of Cardiology

Categories : Cardiovascular DiseaseTags :

Walking Faster Helps Stroke Survivors to Dual-task

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Training stroke survivors to walk faster during recovery can help improve their ability to perform a task at the same time, known as dual-task walking.

Stroke survivors often struggle to walk and perform cognitive tasks at the same time, for example, walking and holding a conversation, or planning what to do next. To effectively walk in the community, cognitive effort is needed to navigate safely and deal with distractions. Many people are unable to regain this ability after a stroke.

Dual-task training ineffective

To improve the ability to walk and think at the same time, rehabilitation approaches have focused on practising walking and at the same performing a task needing cognition, known as dual-task training. Previous research led by Oxford Brookes University and the University of Oxford found that this training did not improve people’s ability to dual-task walk any more than just walking training.

Researchers reasoned that why people struggle with dual-task walking after a stroke may instead be linked to their walking automaticity – the pattern our brains run which means not having to think about walking. This pattern is linked to the cyclic pattern of walking whereby one step ‘signals’ the next step to follow. When walking very slowly, this pattern could be disrupted so that walking is more like independent steps, rather than a cycle.

Faster walkers improved dual-task walking

The new research re-examined the data to compare how slower walkers and faster walkers responded to dual-task training.

“When we compared slower walkers and people who walked at a faster pace – still slower, but closer to walking speeds we expect to see in people who have not had a stroke – both increased their walking speeds after the training,” said Dr Johnny Collett, Senior Clinical Research Fellow in the Centre for Movement, Occupational and Rehabilitation Sciences at Oxford Brookes University.

“However, those who could walk faster at the beginning of the training also improved their ability to walk and think at the same time.”

Advanced brain imaging tracked responses to training

As part of the study, researchers tracked how people’s brains responded to the training using advanced brain imaging. Changes found in the brain supported the findings that stroke survivors who walked slower, had a less automatic control of  walking. Those who walked at a faster pace had changes in the brain consistent with adaptations needed for controlling gait in more complex environments.

“These findings show that, for those who walk slowly, initially focusing on improving walking speed may increase their capacity to improve dual-task walking,” added Dr Collett. “Greater consideration of walking automaticity may help to better tailor intervention and direct a staged approach of increasing complexity to make people better able to walk in the community.”

Importance for rehabilitation

Dr Rubina Ahmed, Director for Research and Policy at the Stroke Association said: “Stroke strikes every 5 minutes and has devastating physical and mental impacts. Whilst four out of five stroke survivors recover the ability to walk, most find it hard outside of hospital which has a big impact on their well-being and independence. By funding this research our charity has helped to highlight that training focused on walking speeds could be an important part of rehabilitation for some stroke survivors’ recoveries. Research like this is key to finding new treatments and improving stroke care, so that stroke survivors can regain the mobility and independence they need to rebuild their lives.”

Source: Oxford Brookes University

Journal reference: Collett, J., et al. (2021) Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial. Clinical Rehabilitation. doi.org/10.1177/02692155211017360.

Categories : Medical Research & TechnologyTags :

India Tests Out Drones for Medical Deliveries

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An aviation firm has carried out the first tests in India of drone deliveries at long ranges, in a step towards one day delivering medicines as well as COVID vaccines to remote areas.

India, with a population of 1.3 billion people spread across some 3.2 million square kilometres is the world’s seventh-largest country by land mass. Experts say that widespread use of drones could be a game-changer for medical services in the South Asian nation’s hard-to-reach rural areas with often poor roads and lack of healthcare infrastructure.

Drones are a cost-effective alternative to road transport in difficult terrains. They can be used in the transport of blood from the blood bank to the place of surgery and that of specimens from hard-to-reach areas to the labs in nearby towns. They can deliver essential medicines like anti-venom for snake bite and dog bite and prevent deaths.

Throttle Aerospace Systems is among 20 organisations granted permits by the government since May to conduct experimental flights beyond the current limit of 450 metres.

Two drones were tested in the southern state of Karnataka: one that can carry up to one kilogramme for 20 kilometres for nearly an hour, and another that can lift two kilogrammes for 15 kilometres.

“Medicines was the payload here and… 2.5 kilometres were covered in seven minutes and it delivered the medicines at the designated point and the drone returned,” Throttle’s co-founder, Sebastian Anto, told AFP at the test site.

This month the Indian government also invited bids from drone operators to help set up a pilot project for the delivering of medical supplies as it seeks to bolster its flagging COVID vaccination drive.

Samiran Panda,  epidemiology chief of the Indian Council of Medical Research, told The Hindu daily newspaper that the technology could help innoculate priority groups in hard-to-reach places.

“We need smart vaccination instead of mass vaccination to stem an epidemic,” Panda told the newspaper last week.

However, India lags behind many other nations when it comes to drones both in terms of their uses and the regulatory framework.Under current regulations, they have to be flown in full view, or within 450 metres, of their operators on the ground.

In Germany, it is reported that researchers are testing drone prototypes that can track down disaster victims by their screams. In Australia, drones using artificial intelligence algorithms are being used to spot crocodiles and count koalas in rugged terrain.

“Drone technology would have a huge impact in those areas where emergency medicines and vaccines could be supplied,” co-founder of lobby group the Drone Federation of India, Vipul Singh, told AFP.

“Where it takes a few hours to travel 20-30 kilometres by road, whereas a drone can actually travel that distance in 10 to 15 minutes,” said Singh, also the co-founder of Bangalore-based Aarav Unmanned Systems.

Source: Medical Xpress

Categories : CancerTags :

FLASH Radiation Treatment for Tumours a Step Closer

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Heavy ion bombardment in FLASH radiation treatment could be the future of radiotherapy, with encouraging findings from a German lab.

The GSI Helmholtzzentrum für Schwerionenforschung and the future accelerator centre FAIR succeeded in performing a carbon ion FLASH experiment for the first time in their Phase 0 experiment. 

The scientists involved were able to achieve the very high dose rates required to irradiate tumours. The success was a collective effort of the GSI Biophysics Department and the accelerator crew on the GSI/FAIR campus in close collaboration with the German Cancer Research Center DKFZ and the Heidelberg Ion Therapy (HIT) center.

FLASH irradiation involves utra-short and ultra-high radiation, delivering the treatment dose in fractions of a second. Traditional radiation therapy, as well as proton or ion therapy, deliver smaller doses of radiation to a patient over an extended time period, whereas FLASH radiotherapy is thought to require only a few short irradiations, all lasting less than 100 milliseconds.

In the field of electron radiation, recent in vivo investigations have shown that the FLASH method’s ultra-high dose rate is less harmful to healthy tissue, but just as efficient as conventional dose-rate radiation to inhibit tumour growth. Such an effect has not yet been demonstrated for proton and for ion beam irradiation, which is the basis of the tumour therapy with carbon ions developed at GSI. There is still a lot of research to be done here. The results of the current experiment at GSI are now being evaluated and will contribute to new knowledge.

There have also been technical barriers to FLASH radiation. Until now, FLASH technique has only been applicable using electron and proton accelerators. While the required dose rates for electrons and protons can be achieved with a cyclotron (circular accelerator), this is more difficult with the synchrotrons required in heavy ion therapy, such as the SIS18 at GSI.

That is why the current FAIR Phase 0 experiment is a very crucial step: Thanks to the improvements at the existing GSI accelerator facility as part of the preparations for FAIR, the necessary dose rate in millisecond range can now also be achieved for carbon ions. However,  much development work remains to be done before this procedure is mature enough to be routinely used on patients in the field of electron radiation.

Professor Marco Durante, Head of the GSI Biophysics Research Department, was very pleased with this important milestone in  the development of FLASH irradiation:

“It is a forward-looking method that could significantly increase the therapeutic window in radiotherapy. I am very happy that the researchers and the accelerator team were able to demonstrate the possibility to create conditions with carbon beams that are necessary for FLASH therapy of tumors. If we can combine the great effect and precision of heavy ion therapy with FLASH irradiation while maintaining efficacy and causing little damage to healthy tissue, this could pave the way of a future radiation therapy several years from now.”

Professor Paolo Giubellino, The Scientific Managing Director of GSI and FAIR, expressed his delight at the results: “The combination of expertise in biophysics and medicine as well as engineering excellence allows the first world-class experiments FLASH irradiation with ion beams to be performed. This could result in important complements to existing radiation therapies. Applications in tumour therapy are one of the research areas that can benefit from the recent increased intensities of GSI accelerators. However, modern radiobiology will substantially benefit from beams with even higher intensities, such as we will have at the FAIR facility currently under construction. FLASH is a first example of these future directions of work”.

Source: GSI Helmholtzzentrum für Schwerionenforschung GmbH

Categories : COVIDTags :

Tech Transfer for Local mRNA Vaccine Production

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South Africa is planning to make vaccines locally using messenger RNA, the breakthrough technology of the global COVID vaccination effort – and once nearly consigned to the dustbin of medical research history.

The World Health Organization (WHO) and its COVAX partners are working with a South African consortium comprising Biovac, Afrigen Biologics and Vaccines, a network of universities and the Africa Centres for Disease Control and Prevention (CDC) to establish its first COVID mRNA vaccine technology transfer hub.

This follows WHO’s global call for Expression of Interest to establish COVID mRNA vaccine technology transfer hubs to scale up production and access to COVID vaccines. The partners will negotiate details with the South African government and public and private partners both local and international.

South African President Cyril Ramaphosa said: “The COVID pandemic has revealed the full extent of the vaccine gap between developed and developing economies, and how that gap can severely undermine global health security. This landmark initiative is a major advance in the international effort to build vaccine development and manufacturing capacity that will put Africa on a path to self determination. South Africa welcomes the opportunity to host a vaccine technology transfer hub and to build on the capacity and expertise that already exists on the continent to contribute to this effort.”

“This is great news, particularly for Africa, which has the least access to vaccines,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “COVID has highlighted the importance of local production to address health emergencies, strengthen regional health security and expand sustainable access to health products.”

The announcement follows the recent visit to South Africa by French President Emmanuel Macron, who gave his country’s commitment to aiding local vaccine production.

“Today is a great day for Africa. It is also a great day for all those who work towards a more equitable access to health products. I am proud for Biovac and our South African partners to have been selected by WHO, as France has been supporting them for years,” said President Macron. “This initiative is the first of a long list to come, that we will keep supporting, with our partners, united in the belief that acting for global public goods is the fight of the century and that it cannot wait.”

Technology transfer hubs are training facilities where the technology is established at industrial scale and clinical development performed. Interested manufacturers from low- and middle-income countries can receive training and any necessary licences to the technology, assisted by the WHO and partners.

Biovac is a bio-pharmaceutical company resulting from a partnership formed with the South African government in 2003 to establish local vaccine manufacturing capability for the provision of vaccines for national health management and security.

Afrigen Biologics and Vaccines is a biotechnology company focuses on product development, bulk adjuvant manufacturing and supply and distribution of key biologicals to address unmet healthcare needs.

The organisations complement one another, and can each take on different roles within the proposed collaboration: Biovac will be the developer while Afrigen is the manufacturer, with a consortium of universities as academic supporters providing mRNA know-how. Africa CDC will provide technical and regional support.

The South African consortium has existing operating facilities with available capacity and experience in technology transfers. It is also a global hub that can start training technology recipients immediately.

The WHO is speaking to a number of pharmaceutical manufacturers about establishing the hub, though the talks are so far mainly with “smaller companies,” said Soumya Swaminathan, WHO’s chief scientist. “We are having discussions with the larger companies with proven mRNA technology,” she added.

The mRNA vaccines may be produced in South Africa within 9 to 12 months, she said. WHO’s call for expressions of interest has so far generated 28 offers to either provide technology for mRNA vaccines or to host a technology hub or both. 

It is the first time that messenger RNA technology has been used to make vaccines, which has been used by Moderna and Pfizer/BioNTech. They have proven very effective against the original SARS-CoV-2 strains and even against its more recent variants.

Source: World Health Organization

Categories : Medical Research & TechnologyTags :

‘Windscreen Wiper’ Tool for Laparoscopes Allows Uninterrupted View

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A Brigham Young University student has developed a ‘windscreen wiper’ tool for laparoscopes that continuously keeps the camera end clean.

The laparoscope, a slender rod with a camera tip, allows doctors to see inside a body during surgery. Laparoscopes have made surgery less invasive and easier for surgeons and patients, but the device does have a problematic drawback: it must be removed, cleaned, and reinserted multiple times during surgery.

Engineering graduate student Jacob Sheffield has developed a tiny origami-based device that serves as a miniature windshield wiper for laparoscope camera lenses. When installed, the device eliminates the need to remove and reinsert laparoscopes every five or so minutes during surgery, which would allow surgeons to focus on the patient without disruptions.

“It’s like driving the car in the rain,” Sheffield explained. “If you can focus on driving and not on reaching out the window to wipe off the windshield with your hand, you can keep your focus on what’s important.”

His technology, developed with mentoring from BYU professor Larry Howell in the Compliant Mechanisms Research Lab and help from ME undergrad Amanda Lytle, is called LaparoVision. The disposable mechanism snaps on to existing laparoscopes and features a one-piece curved wiper that conforms to the cylindrical walls of the medical tool. The wiper, which is so small it can rest on the end of a finger, is actuated by a trigger outside of the body.

The innovative concept was impressive enough to earn Sheffield the title of 2021 Student Innovator of the Year at BYU, an award which also provides kickstarter money to develop a project.

“It’s extremely helpful to get that funding through BYU awards programs and the feedback you get from judges is invaluable,” Sheffield said. “My advice for future applicants is even if you don’t win or get money out of it, use the deadline of the competitions to drive progress for your idea.”

For Sheffield, the idea came about when he was meeting with surgeons across the country on other medical technologies being tested in the CMR lab. The issue of laparoscope removal and cleaning kept coming up in their conversations. The tool is used in 5 million surgeries every year in the US alone, and in roughly 90% of those procedures, the device must be removed.

Sheffield said that, according to many surgeons and studies, every five to eight minutes the device has to be pulled out and the lens wiped clean. With operating rooms costing $62 a minute, those fairly regular removals prove costly and frustrating. However, even more importantly, withdrawal of the scope at a critical time can cause serious risks for the patient.

“There is a high correlation in keeping the scope clean, maintaining surgical focus and ensuring timely and safe patient outcomes,” Sheffield said. “But it’s not just about improving efficiency during surgery; every time you lose vision it could be a critical part in the surgery where you make an incision and get blood on the lens and you can’t see what’s going on.”

Sheffield is currently in talks to license the technology and has now formed a startup (Bloom Surgical) to bring the device to market. Currently he is focusing on showing that the device is reliable and sage, and working towards getting FDA clearance for the tool.

Source: Brigham Young University

Categories : GenderTags :

Bias Against Both Sexes Found in Clinical Trials

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Though evenly split overall, research shows that women and men in disease trials are not represented according to the population affected.

Clinical trial sample populations should be proportionate to the population affected by the disease, as some diseases are more prevalent or manifest differently in one sex versus the other. Neglecting one sex in clinical trials can skew medical evidence toward therapies for the neglected population.
The study cross-analysed over 20 000 US clinical trials between 2000-2020, and found that women are underrepresented in clinical trials in cardiology, oncology, neurology, immunology and haematology. Meanwhile, men are underrepresented in clinical trials in musculoskeletal disease and trauma, psychiatry and preventive medicine. 

This study, published JAMA Network Open, is the first to examine sex bias in all US human clinical trials relative to disease burden (which is the prevalence of disease based on factors such as sex and ethnicity).

“Sex bias in clinical trials can negatively impact both men and women by creating gendered data gaps that then drive clinical practice,” said first study author Dr Jecca Steinberg, a medical resident in the department of obstetrics and gynecology at Northwestern University Feinberg School of Medicine. “Neglecting one sex in clinical trials — the gold standard scientific exploration and discovery — excludes them from health innovation and skews medical evidence toward therapies with worse efficacy in that sex.”

Underrepresentating either sex in clinical trials can lead to less optimal health outcomes; differences exist for women and men in medical test results, disease progression, treatment response, drug metabolism and surgical outcomes, Dr Steinberg said.

These differences stem from variations in body size, composition, and hormones. Women’s smaller body sizes and higher fat contents typically result in varied drug responses. One study showed that aspirin has differential effects on the sexes with regard to primary protection against strokes and heart attacks. Aspirin only lowered women’s risk of stroke but had no effect on the risk of myocardial infarction or death.

“Identifying areas of research in which sex bias disadvantages males is important to improving population health,” Dr Steinberg said. “Our novel finding that men are underrepresented in trials related to mental health and trauma assumes greater urgency in American society where suicide, violence and substance use increasingly contribute to growing morbidity and premature male mortality in the US.”

Clinical trials for preventative medicine are more likely to have greater enrollment of women, the study found, adding credence to the notion that women, more than men, seek out preventive services and access to health care.  

Women-specific underrepresentation remains
“One of the top reasons for Food and Drug Administration drug recall is adverse effects in women,” Dr Steinberg said. “Millions and millions of dollars go into these trials, so to relatively neglect women in the trial population is a waste.

“A greater allocation of resources for female-focused trials could be critical to improving care for women and discerning the heterogenous manifestations of diseases within the female population.”

For example, women with heart disease often have different reactions to medications and experience different symptoms from men, such as feeling abdominal pain rather than their left arm. If a clinical trial implements its intervention based on symptoms predominantly exhibited by the male population, it could miss testing interventions in women with cardiac arrest. 

The reduced representation of women relative to disease burden specifically in oncology and cardiology clinical trials is especially troubling, said Steinberf, because cardiologic and oncologic diseases are among the leading causes of death among women in the US.

Participating in clinical trials is also one of the only ways to access cutting edge therapies, especially oncology, so the relative deficiency of one sex contributes to disparities in health outcomes, Steinberg said.  

“One of our hopes from this study is that scientists and physicians will read about our findings and be inspired to say, ‘Why is that happening in my field?’ and then address it,” Dr Steinberg said.

Source: Northwestern University

Categories : COVID GastrointestinalTags :

Common Gut Bacteria Could Inhibit SARS-CoV-2

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Bifidobacterium eriksonii, stained with fluorescent antibodies. Source: Public Health Image Library

South Korean researchers have found that certain common gut bacteria produce compounds that inhibit SARS-CoV-2. 

The research was presented on June 20 at World Microbe Forum, an online meeting of the American Society for Microbiology (ASM), the Federation of European Microbiological Societies (FEMS), and several other societies that taking place online June 20-24.

Previous clinical findings had shown that some patients with moderate to severe COVID experience gastrointestinal symptoms, while others show signs of infection in the lungs only.

“We wondered whether gut resident bacteria could protect the intestine from invasion of the virus,” said Mohammed Ali, a PhD student in Medicine at Yonsei University in South Korea.

To investigate this hypothesis, the researchers screened dominant bacteria inhabiting the gut for activity against SARS-CoV-2. Their efforts revealed that Bifidobacteria, already shown to suppress other bacteria such as H. pylori and have proven active against irritable bowel syndrome, had such activity, said Ali. Bifidobacteria are common in the guts of breast fed infants, which is partly driven by the bifidogenic activities of specific mother milk-derived oligosaccharides

The researchers also searched for potential illness-fighting compounds in databases containing microbially produced molecules, and discovered some that might also be useful against SARS-CoV-2. “To train our model we leveraged previous coronavirus datasets in which several compounds were tested against targets from coronaviruses,” explained Ali. “This approach seems to be significant as those targets share features in common with SARS-CoV-2.”

Ali emphasised the ecological nature of his approach to this work, pointing out that numerous existing antibiotics and cancer therapies are themselves compounds that bacteria use to compete with each other within the gastrointestinal tract, and that these were initially purified from microbial secretions.

“Finding microbes that secrete anti-coronavirus molecules will be a promising method to develop natural or engineered probiotics to expand our therapeutics prevention techniques, to provide a more sustainable way to combat the viral infection,” said Ali.

Source: American Society for Microbiology

Categories : COVIDTags : 1 Comment

Brazil COVID Deaths Pass Half a Million

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Brazil’s COVID deaths passed 500 000 in Brazil, days after the US reported passing 600 000 deaths. Experts warn of a worsening outbreak amid slow vaccination and the onset of winter.

President Jair Bolsonaro refuses to back measures like social distancing even as the virus continues to take its toll. With only 11% of adults vaccinated, Brazil’s health institute Fiocruz says the situation is “critical”.

Heavy criticism has been directed at President Bolsonaro for not implementing a co-ordinated national response and for his vaccine scepticism, lockdowns and mask-wearing requirements, which he has sought to loosen.

The country has reported, on average, 70 000 cases and 2 000 deaths daily in the past week. Most new cases were among those aged 20-59, Fiocruz said, warning that the start of winter in the southern hemisphere this week could result in more infections.

Yet governors and mayors have already relaxed nonpharmaceutical interventions. Restaurants, bars and shops have reopened in many cities, while many people in the streets are not wearing face masks or following social distancing.

“People in Brazil are tired and they normalise death now,” Dr Natalia Pasternak Taschner, a microbiologist at the Question of Science Institute, told the BBC, adding that they have a long way to go.

“If we’re not successful in changing the behaviour of people and if we don’t have campaigns for mask wearing, social distancing and vaccinations coming directly from the central government we’re not going to be able to control it.”

On Saturday, protests against President Bolsonaro were held in cities across the country, with demonstrators accusing him of delaying the purchase of vaccines yet prioritising unproven treatments, such as hydroxychloroquine.

More transmissible variants of the virus have driven Brazil’s outbreak, including the one first identified in the Amazon region which is now known as Gamma. Occupancy rate for intensive care unit beds remains at or above 80% in most states, while cities struggle with vaccine supplies.

Faced with a crumbling healthcare system without the relief of lockdowns, a ‘Covid Kit‘ of ivermectin and azithromycin has been touted by the government, and which is widely prescribed. Ironically, its creator, a doctor in Mato Grosso state, died of COVID last September. In a country notorious for its excessive pill-taking, doctors are finding it difficult to recruit people into trials who have not taken ivermectin.

The Brazilian Senate is looking into President Bolsonaro’s handling of the pandemic. The opposition is accusing him of delaying vaccine orders for political reasons, as he has consistently downplayed the pandemic’s severity.

But President Bolsonaro maintains he has done all he can to buy vaccines from several countries, and insists the impacts of a lockdown would be worse than the pandemic.

The president has not commented on the 500 000 deaths although on Twitter, Health Minister Marcelo Queiroga expressed solidarity with relatives of those who had died.

Source: BBC News

Categories : AntibioticsTags :

Disarming a Common Pathogenic Bacterium

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Pseudomonas aeruginosa bacteria. Source: Public Health Imagery Library

Scientists have discovered a gene regulator in a common pathogenic bacterium that can be exploited to drastically reduce its virulence.

Pseudomonas aeruginosa is a gram-negative, aerobic, opportunistic, pathogenic bacterium found in a variety of ecological niches, such as plant roots, stagnant water or even plumbing. Naturally extremely versatile, it can cause acute and chronic infections that are potentially fatal for immunocompromised hosts. P. aeruginosa poses a serious threat in clinical settings, where it can colonise respirators and catheters. Additionally, its adaptability and resistance to many antibiotics make P. aeruginosa infections steadily more difficult to treat. Therefore new antibacterials are urgently needed. 

Scientists from the University of Geneva (UNIGE) in Switzerland have identified a previously unknown regulator of gene expression in this bacterium, without which the infectious power of P. aeruginosa is diminished. This discovery may unlock new developmental pathways to treat this bacteria.

RNA helicases perform essential regulatory functions by binding and unwinding various RNA molecules to perform their functions. RNA helicases are present in the genomes of almost all known living organisms, including bacteria, yeast, plants, and humans; however, they have acquired specific properties depending on the organism in which they are found. “Pseudomonas aeruginosa has an RNA helicase whose function was unknown, but which was found in other pathogens”, explained Martina Valentini,  a researcher leading this research in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine. “We wanted to understand what its role was, in particular in relation to the pathogenesis of the bacteria and their environmental adaptation.”

A severely reduced virulence

To accomplish this, the researchers took a combined biochemical and molecular genetic approach. “In the absence of this RNA helicase, P. aeruginosa multiplies normally in vitro, both in a liquid medium and on a semi-solid medium at 37°C”, reported Stéphane Hausmann, a researcher associate in the Department of Microbiology and Molecular Medicine at UNIGE Faculty of Medicine and first author of this study. “To determine whether the infection capacity of the bacteria was affected, we had to observe it in vivo in a living organism.”

The scientists then continued their research using Galleria mellonella larvae, a model insect for studying host-pathogen interactions.These larvae can live at temperatures between 5°C and 45°C, which makes it possible to study bacterial growth at different temperatures, including that of the human body. Three groups of larvae were observed, including a control group injected with saline. In the presence of a normal strain of P. aeruginosa, less than 20% survived at 20 hours after infection. In contrast, when P. aeruginosa lacked the RNA helicase gene, over 90% of the larvae remained alive. “The modified bacteria became almost harmless, while remaining very much alive,” says Stéphane Hausmann.

Inhibiting instead of killing

The findings demonstrated that the regulator affects production of several virulence factors in the bacteria. “In fact, this protein controls the degradation of numerous messenger RNAs coding for virulence factors”, summarised Martina Valentini. “From an antimicrobial drug strategy point of view, switching off the pathogen’s virulence factors rather than trying to eliminate the pathogen completely, means allowing the host immune system to naturally neutralise the bacterium and potentially reduces the risk for the development of resistance. Indeed, if we try to kill the bacteria at all costs, the bacteria will adapt to survive, which favours the appearance of resistant strains.”

The Geneva team is continuing its investigations by screening drug molecules to see if any of them can selectively block this protein, and also performing a detailed study in detail on the inhibition mechanisms on which could be based the development of an effective therapeutic strategy.

Source: University of Geneva

Journal reference: Hausmann, S., et al. (2021) The DEAD-box RNA helicase RhlE2 is a global regulator of Pseudomonas aeruginosa lifestyle and pathogenesis. Nucleic Acid Research. doi.org/10.1093/nar/gkab503.