Tag: 22/6/21

Categories : GastrointestinalTags :

Macrophage Role in Liver Regeneration Identified

On By ModernMedia
A macrophage engulfing a yeast cell. Source: CDC

Researchers have found out what role macrophages play in liver regeneration after resection. The results are published in the journal Biomedicine & Pharmacotherapy.

In mammals, the liver is the most regenerative internal organ. It can restore its original size with as little as 25% of the original tissue remaining. Macrophages play an important role in this process. It is known, for example, that if the liver is affected by foreign substances, including drugs, macrophages migrate to the liver, absorb harmful microorganisms and dead cells, cause inflammation and thus contribute to the restoration of the organ. However, it is still unknown unambiguously how macrophages affect the growth of the liver after its resection, ie when a large part of the organ is removed. RUDN University doctors investigated this issue in an experiment with laboratory mice.

“The role of macrophages in the liver growth after massive resections is uncertain. Some studies reveal the lack of immigration of macrophages to the liver during its recovery from partial resection, whereas other studies demonstrate such possibility. So, we focused our study on the macrophage population dynamics after 70% liver resection in mouse mode”, Andrey Elchaninov, MD, PhD, researcher at the Department of Histology, Cytology and Embryology of RUDN University.

The researchers removed 70% of the liver of a number of lab mice. Immediately after that, then a day later, three days later, and a week later, the scientists took liver samples for analysis. The resulting cells were studied using an immunohistochemical method. The sections were labelled with specific antibodies to the glycoproteins CD68, CD206 and other compounds that are found on the surface of macrophages. To count them, the antibodies are labelled with fluorescent dyes and glow when attached to macrophages. The researchers also measured the rate of reproduction and cell death of macrophages.

The researchers found that after resection, macrophages migrate to the liver in large numbers. A day after surgery, the number of macrophages with CD68 in the liver doubles, which persists after a week. It also turned out that the resection led to significant changes in the ratio of different types of macrophages. For example, the proportion of Ly6C cells in the week after surgery increased 4-fold — from 5% to 22%, and the proportion of CD86 droppedfrom 50% to 15%. The role of macrophages is ambiguous. On the one hand, they release chemicals (chemoattractors) that attract white blood cells responsible for the body’s inflammatory response, but on the other hand, they regulate the reproduction of liver cells and the metabolism in the organ.

“Corresponding profiles of macrophages in the regeneration of the liver cannot be unambiguously defined as pro- or anti-inflammatory,” the researchers said. “Their typical features include elevated expression of leukocyte chemoattractant factors, and many of the differentially expressed sequences are related to the control of cell growth and metabolic processes in the liver. Our findings revealed essential roles of macrophages and macrophages proliferation in the mouse liver during its recovery from a massive resection.”

Source: EurekAlert!

Journal reference: Elchaninov, A., et al. (2021) Macro- and microtranscriptomic evidence of the monocyte recruitment to regenerating liver after partial hepatectomy in mouse model. Biomedicine & Pharmacotherapy. doi.org/10.1016/j.biopha.2021.111516.

Categories : Cardiovascular Disease NeurologyTags :

Statins not Associated With Cognitive Decline

On By ModernMedia
Photo by Matteo Vistocco on Unsplash

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

On By ModernMedia
Photo by bennett tobias on Unsplash

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

On By ModernMedia
Photo by Thomas Bjornstad on Unsplash

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