Study reveals how red blood cells may help stave off aging

 

• Reduced oxygen supply to tissues may be partly responsible for age-related physical and cognitive decline.
• A receptor in the membrane of red blood cells is known to promote the release of oxygen from hemoglobin at high altitudes.
• A new study in mice found that the same receptor mitigates the cognitive decline and hearing loss associated with aging by improving oxygen supply to tissues.
• The discovery provides potential targets for new anti-aging drugs.

Between 1960 and 2015, average life expectancy at birth increased by a decade in the United States, from 70 to 79 years of age, and is expected to rise still further.

While this reflects the success of modern medicine, it also means that an increasing proportion of the population has to live with the physical and cognitive deterioration that comes with old age.

Finding new ways to help people age well, and not just live longer, has become a priority.

One clue to achieving this lies in the idea that aging is accompanied by a decrease in the supply of oxygen to tissues. Researchers suggest that this triggers immune changes that promote chronic inflammation, which is linked to almost all conditions of old age.

Among the many potential consequences of this “inflammaging” could be cognitive decline and hearing loss.

There is, however, evidence that improving oxygen supply can reverse some cellular signs of aging. For example, one small study found that hyperbaric oxygen therapy, which is a treatment that involves breathing almost pure oxygen, appeared to rejuvenate immune cells in older adults.

Another study found that red blood cells respond to the low-oxygen conditions of high altitudes by increasing the amount of oxygen they deliver to tissues. They do this through increased signaling by a receptor in their membrane, known as the adenosine receptor A2B or ADORA2B, which promotes the release of oxygen by hemoglobin.

Aging in general, but particularly some neurodegenerative conditions such as Alzheimer’s disease, is associated with reduced activity in the same metabolic pathway.

Now, research in mice led by the University of Texas McGovern Medical School in Houston has found that ADORA2B also appears to stave off some of the effects of aging by increasing oxygen supply to tissues.

In theory, a drug that increases activity in this pathway could help combat age-related declines.

“So far, there is no such drug available,” Dr. Yang Xia, who led the study, told Medical News Today.

However, she also noted that the discovery that hyperbaric oxygen treatment can reverse some of the effects of aging on human blood cells suggests that it might work.

“Our finding immediately highlights that enhancing O2 [oxygen] delivery mediated by ADORA2B signaling is likely a new rejuvenating approach,” she said.

The research appears in the journal PLOS Biology.

Accelerated aging

The scientists studied mice genetically engineered to lack ADORA2B in the membranes of their red blood cells.

These animals appeared to age at a younger age than normal mice. They also experienced steeper declines in their spatial learning, memory, and hearing abilities.

On a cellular level, the rodents showed signs of inflammaging, including increased production of pro-inflammatory cytokines, or signaling molecules that encourage inflammation.

“Our findings reveal that the red blood cell ADORA2B signaling cascade combats early onset of age-related decline in cognition, memory and hearing by promoting oxygen delivery in mice and immediately highlight multiple new rejuvenating targets,” says Dr. Xia.

However, more research is needed to determine whether ADORA2B levels decline with age in normal mice, and whether drugs that activate the ADORA2B pathway can slow down age-related loss of hearing and cognition.

Studies in humans may also be on the cards.

“We plan to validate our mouse finding in humans in the near future,” Dr. Xia told MNT.

One of the limitations of studying aging by conducting experiments in animals such as mice and fruit flies is that their life spans are so much shorter than ours.

Humans are already evolutionarily adapted to live longer than these creatures, so the potential for any further gains in healthy life spans may be more limited.

Immune aging and how to combat it

With age, the human immune system becomes less effective at tackling infections and less responsive to vaccinations. At the same time, the aging immune system is associated with chronic inflammation, which increases the risk of almost all conditions linked to old age.

The good news is that exercising and adopting the right diet may help a person maintain healthy immunity into older age.

Chimpanzees and gorillas, our closest primate relatives, live for only 10–15 years in the wild once they have reached maturity. After the human evolutionary lineage split from theirs, our ancestors’ life expectancy doubled over the next 5 million years.

Scientists believe that it remained relatively stable into the 18th century. In the 250 years between then and now, however, life expectancy more than doubled again due to improvements in sanitation and healthcare.

We live in a time of high average life expectancies. However, our long evolutionary history has adapted us for different lifestyles (and even life expectancies), and these have changed drastically.

As a result, immunity not only weakens in older age; it also becomes imbalanced. This affects the two branches of the immune system — “innate” immunity and “adaptive” immunity — in a double whammy of “immunosenescence.”

“Innate” immunity, which is our first line of defense against infections, fails to resolve after the initial threat has passed, causing chronic, systemic inflammation.

“Adaptive” immunity, which is responsible for remembering and attacking particular pathogens, steadily loses its ability to defend against viruses, bacteria, and fungi.

Chronic, low-grade inflammation is associated with almost all conditions linked to older age, including type 2 diabetes, cardiovascular disease, cancer, and dementia. It also plays a leading role in certain autoimmune conditions that are more common in older adults, such as rheumatoid arthritis.

Meanwhile, the loss of adaptive immunity that comes with older age not only makes people more susceptible to infections; it can also reactivate dormant pathogens that were previously suppressed.

In addition, the weaker adaptive immunity of older adults means that their bodies respond less strongly to vaccinations, such as the annual flu shot.

Source: Medical News Today

COVID-19-related multisystem inflammatory syndrome not exclusive to children

 

• Doctors diagnose multisystem inflammatory syndrome primarily in children, but it can also occur in older individuals.
• Healthcare providers should suspect the syndrome in adults with elevated inflammatory symptoms.
• While the illness is serious, prompt treatment can prevent severe outcomes.

New information continues to materialize on the aftereffects of COVID-19. Reported complications from the COVID-19 disease include blood clots, cardiovascular disease, kidney or liver injury, and post-COVID-19 syndrome.

Multisystem inflammatory syndrome is another serious complication that healthcare professionals see in some childrenTrusted Source testing positive for COVID-19.

While health professionals saw this rare but potentially severe COVID-19-related illness in younger patients initially, it has not proven exclusive to children. There have been a small number of adults younger than 50 years of age who have been diagnosed with this inflammatory syndrome.

Infectious disease specialists at the University of Calgary in Alberta recently published a case in the Canadian Medical Association Journal suggesting that age should not limit the potential diagnosis of multisystem inflammatory syndrome in adults.

Symptoms shown by an older patient

Doctors Geneviève Kerkerian and Stephen D. Vaughan, authors of the case, reported that a 60-year-old man was diagnosed with the inflammatory condition.

The patient, who had tested positive for SARS-CoV-2 four weeks earlier, visited the hospital with a range of symptoms, including mild shortness of breath, profound fatigue, loss of appetite, a high fever, and a swollen lymph node.

During the exam, his doctors also noted his red eyes, swollen tongue, and a red blush at the end of his toes.

He did not have the more commonly reported symptoms of multisystem inflammatory syndrome such as stroke, shock, or cardiac dysfunction.

The doctors attributed this to either him having had a milder case of COVID-19 or the prompt diagnosis and interventions he received once at the hospital.

Diagnosing multisystem inflammatory syndrome in adults

Accurately diagnosing the syndrome has proven challenging. “It’s a little bit tricky to diagnose,” Dr. William Schaffner, Professor of Infectious Diseases at Vanderbilt University Medical Center in Nashville, Tennessee, told Medical News Today. Dr. Schaffner was not involved in the research.

There is no single diagnostic test that will definitively indicate the presence of the syndrome. Schaffner compared diagnosis of the syndrome to putting together the pieces of a puzzle until reaching that “ah-ha” moment.

Symptoms of multisystem inflammatory syndrome are similar to those of the hyperinflammatory condition known as Kawasaki disease, which also primarily affects young children.

The American College of Rheumatology published a review comparing symptoms between multisystem inflammatory syndrome in children and Kawasaki disease. Of the children who met the diagnostic criteriaTrusted Source for the syndrome, 25–50% also fulfilled the requirements for Kawasaki disease.

The male patient from the case study also met the criteria for Kawasaki disease. However, his recent contraction of the SARS-CoV-2 infection and age led doctors to look deeper into the possibility of multisystem inflammatory syndrome. Further testing showed an enlarged heart and a swollen lung. For this patient’s doctors, this was the “ah-ha” moment.

“Given the patient’s recent history of SARS-CoV-2 infection, fevers without localizing symptoms, oral mucosal changes, cervical lymphadenopathy, conjunctivitis, and lower extremity changes, we suspected inflammatory post-COVID-19 syndrome,” wrote Kerkerian and Vaughan.

The patient received treatment with aspirin and steroids. After 24 hours, he began to show signs of reduced inflammation in the eyes, tongue, and toes. His doctors discharged him after 5 days with a repeat electrocardiogram showing normal.

Increasing awareness within the medical community

While multisystem inflammatory syndrome in children is rare, it is common enough that pediatricians are on high alert for this condition in patients testing positive for SARS-CoV-2. However, much is unknown about the syndrome in adults.

“It is critical that those who care for adults — the internists, family doctors, specialists, nurse practitioners, have a sense of this syndrome so that it can be recognized, diagnosed, and appropriately treated,” said Schaffner.

Optimal follow-up for multisystem inflammatory syndrome is currently unknown. However, experts agree that monitoring for coronary artery dilatation and aneurysm should play a major role.

The authors conclude by noting, “Unlike for MIS-C (multisystem inflammatory syndrome in children), there is currently no requirement to report cases of MIS-A (multisystem inflammatory syndrome in adults) to provincial or state authorities, but this should be encouraged to facilitate research and improve patient outcomes.”

Source: Medical News Today

COVID-19: Which vaccines are effective against the delta variant?

 Scientists are studying how well COVID-19 vaccines work against the delta variant of SARS-CoV-2. We discuss the latest findings.

The delta variant of SARS-CoV-2, which was first identified in India, is now the dominant form of the virus in the United Kingdom. In the United States, at least 10% of new cases are with this variant.

Data from the U.K. show that new SARS-CoV-2 infections have increased by 31% in the past 7 days. Moreover, an analysis from Public Health England (PHE) suggests that the delta variant is more transmissible than previous ones and that it is more likely to lead to treatment in the hospital.

Yet recent data indicate that vaccines are effective at preventing severe COVID-19 caused by the delta variant that would require hospital treatment.

In this article, we present up-to-date research on how well COVID-19 vaccines work against the delta variant.

‘Very high levels of protection against hospitalization’

A recent analysis from PHE looks at how likely people who had an infection with the delta variant were to need treatment in the hospital.

The report puts the protection from requiring hospital treatment for COVID-19 at 71% after one dose and at 92% after two doses of the Oxford-AstraZeneca vaccine. The Pfizer vaccine was 94% effective at preventing hospitalization after the first dose and 96% after two doses.

In India, the Oxford-AstraZeneca COVID-19 vaccine bears the name Covishield.

The report, which has not been peer-reviewed yet, puts these percentages on a par with protection against the alpha variant, or B.1.1.7, which scientists first identified in the U.K.

“These findings indicate very high levels of protection against hospitalization with the delta variant with one or two doses of either vaccine,” the authors write.

It comes after an earlier report that indicates COVID-19 vaccines were less effective at protecting people from COVID-19 if they had only received the first dose of the Pfizer-BioNTech or Oxford-AstraZeneca vaccines.

However, in the analysis, which has not yet undergone peer review, the researchers measured any symptomatic case of COVID-19, regardless of severity.

Covaxin data

There is next to no data on how other COVID-19 vaccines are faring against the delta variant at this stage.

A small research study, not yet peer-reviewed, from scientists at the Indian Council of Medical Research and Bharat Biotech International, who co-developed the Covaxin COVID-19 vaccine, reports on its effectiveness against the delta variant.

The researchers found that antibodies from vaccinated individuals were not as effective at neutralizing the virus variant in a lab study. Despite this, they write that the vaccine’s “neutralization potential is well established.” They attribute this to the way the vaccine works.

Covaxin is made from the entire SARS-CoV-2 virus, chemically altered to prevent it from replicating.

When a person receives the vaccine, they can make antibodies to many different parts of the virus. If one part mutates to give rise to a new variant, such as the delta variant, then antibodies to other parts of the virus should still confer enough protection.

However, the study was small, and further research is necessary to look at how effective the Covaxin COVID-19 vaccine is in real-life settings at preventing severe COVID-19 from the delta variant.

Sputnik V and CoronaVac

The makers of the Russian Sputnik V COVID-19 vaccine recently announced on Twitter that their vaccine was more effective against the delta variant than others. They added that they had submitted the data to an international peer-reviewed journal.

The company also said that it would soon be offering a booster shot specifically designed to work against the delta variant.

Until such time as the data are publicly available, it is not possible to assess the validity of these statements about the Sputnik V vaccine.

There is also little data available about how effective the Sinovac COVID-19 vaccine (CoronaVac) is against the delta variant. A recent Reuters news piece reports that over 350 doctors and medical staff in Indonesia developed COVID-19 despite receiving CoronaVac.

According to the report, “Most of the workers were asymptomatic and self-isolating at home, said Badai Ismoyo, head of the health office in the district of Kudus in central Java, but dozens were in hospital with high fevers and falling oxygen saturation levels.”

The region is seeing high numbers of infections, which experts believe are mostly due to the delta variant. Given the Reuters report, it is clear that more research is needed to establish exactly how well CoronaVac can protect from severe COVID-19 due to the delta variant.

Source: Medical News Today

How likely is England to achieve zero new HIV cases by 2030?

 

• England may be on track to eliminate HIV as a public health concern by 2030.
• New research looked at the likelihood of England reaching this goal among men who have sex with men (MSM).
• The study authors highlight the need for better ways to reduce numbers of new HIV infections among men aged 45 and older.

In 2014, the United Nations developed a strategy for addressing the HIV epidemic, and this set out “90-90-90 targets.”

These targets aim for three things. The first is for 90% of people with HIV to be aware of their status. The second is for 90% of people who know their HIV status to be receiving antiretroviral therapy. The third target is for 90% of people taking antiretroviral therapy to have achieved “viral suppression,” which means having fewer than 200 copiesTrusted Source of the virus per milliliter of blood.

England achieved these targets in 2017 and set an ambitious new goal of ending HIV transmission by 2030.

A recent study in The Lancet HIVTrusted Source looked at the likelihood of England reaching its goals and reducing HIV transmission among MSM so that it becomes exceedingly rare.

The researchers also analyzed data to determine the effects of several intervention strategies on the spread of HIV. With the help of historical data and novel computational modeling, the study authors have identified encouraging trends.

Their analysis suggests an overall likelihood of 40% that England will succeed by 2030. The authors also note the need to target specific age groups, in which the number of new HIV infections has not declined to the same extent as in other groups.

Drop in new cases

The team, led by researchers from the University of Cambridge, in the United Kingdom, used a novel mathematical model that allowed them to estimate the numbers of new HIV infections between 2009 and 2018.

Researchers use modeling because there is often a time lag between a person contracting HIV and receiving the diagnosis. The model allowed the scientists to estimate the incidence of new HIV infections, including those that go undiagnosed, among MSM aged 15 or older.

The researchers point to reasons for cautious optimism. They found an across-the-board decrease in HIV infections within the study population.

According to the model, new HIV infections fell from 2,770 in 2013 to 854 in 2018.

All age groups showed reductions in HIV infection rates, but in the group aged 45 and over, the rate decline was the slowest. The authors suggest a need for targeted policies to further slow the rate of new cases among this group.

Based on the data, the team predicts a 40% probability that England will achieve fewer than one new HIV infection per 10,000 people by 2030.

Winning strategies

In their study, the researchers were not able to link results with specific public health strategies implemented in the last decade. However, they do find support for these strategies in the data.

Starting in 2011, test-and-treat measures gained significant traction. Specific approaches that appear to have had a positive effect include enhanced testing, early treatment, and treatment-as-prevention, including preexposure prophylaxis (PrEP).

PrEP became widely available in 2016 and is “now considered the best strategy to prevent HIV transmission” among MSM, the authors explain.

“This is very good news and suggests that prevention measures adopted in England from 2011 have been effective. With the rollout of PrEP, England looks on course to meet the goal of zero transmissions by 2030,” senior study author Professor Daniela De Angelis comments.

“Our study also shows the value of regular estimation of HIV incidence to recognize and respond appropriately to changes in the current downward trend. The challenge now is to achieve these reductions in all groups at risk for HIV acquisition,” she continues.

The researchers point out several limitations of their study. One is that they were unable to account for people moving away, nationally or internationally.

Despite the limitations, the authors conclude that “With additional large-scale implementation of PrEP, elimination of HIV transmission is likely to be within reach by 2030. However, targeted combination prevention measures might be needed to maintain the trajectory toward elimination in groups such as MSM aged 45 years or older.”

Dr. Valerie Delpech, the head of national HIV surveillance at Public Health England, which partly funded the study, commented on its findings:

“We have made good progress toward ending HIV transmission by 2030 in England. Frequent HIV testing and the use of PrEP among people most at risk of HIV, together with prompt treatment among those diagnosed, are key to ending HIV transmission by 2030.”

Takudzwa Mukiwa, the head of health programs at the Terrence Higgins Trust, a U.K.-based HIV and sexual health charity, told Medical News Today, “The reality is, we now have all the tools we need to end new HIV cases in the U.K. by 2030 — not just among gay and bisexual men, as discussed in this study, but across all groups impacted by HIV.”

“We have prevention pill PrEP that stops [people] from contracting HIV, a range of fast testing options, and effective treatment for people living with HIV that means the virus can’t be passed on.”

“But we mustn’t be complacent, and we will only get there by making a real step change to ensure that we see a fall in HIV cases across all groups, rather than just those traditionally most impacted,” Mr. Mukiwa emphasized.

He also commented on the need for the British government to implement a robust strategy to achieve the goal of zero new cases by 2030.

“The government has committed to ending domestic HIV transmissions by the end of the decade and is currently drafting its action plan for making it happen. We are holding [the] government to account on its promise and must see an ambitious, properly resourced plan published this summer,” Mr. Mukiwa said.

“It must include PrEP being made available outside sexual health clinics with access via [general practitioner] surgeries and in pharmacies. We also want to see free postal testing available throughout the year and more testing as standard across our [National Health Service].”

Source: Medical News Today

 Tools that allow neuroscientists to record and quantify functional activity within the living brain are in great demand. Traditionally, researchers have used techniques such as functional magnetic resonance imaging, but this method cannot record neural activity with high spatial resolution or in moving subjects. In recent years, a technology called optogenetics has shown considerable success in recording neural activity from animals in real time with single neuron resolution. Optogenetic tools use light to control neurons and record signals in tissues that are genetically modified to express light-sensitive and fluorescent proteins. However, existing technologies for imaging light signals from the brain have drawbacks in their size, imaging speed, or contrast that limit their applications in experimental neuroscience.

A technology called light-sheet fluorescence imaging shows promise for imaging brain activity in 3D with high speed and contrast (overcoming multiple limitations of other imaging technologies). In this technique, a thin sheet of laser light (light-sheet) is directed through a brain tissue region of interest, and fluorescent activity reporters within the brain tissues respond by emitting fluorescence signals that microscopes can detect. Scanning a light sheet in the tissue enables high-speed, high-contrast, volumetric imaging of the brain activity.

Currently, using light-sheet fluorescence brain imaging with nontransparent organisms (like a mouse) is difficult because of the size of the necessary apparatus. To make experiments with nontransparent animals and, in the future, freely moving animals feasible, researchers will first need to miniaturize many of the components.

A key component for the miniaturization is the light-sheet generator itself, which needs to be inserted into the brain and thus must be as small as possible to avoid displacing too much brain tissue. In a new study reported in Neurophotonics, an international team of researchers from the California Institute of Technology (USA), University of Toronto (Canada), University Health Network (Canada), the Max Planck Institute of Microstructure Physics (Germany), and Advanced Micro Foundry (Singapore) developed a miniature light-sheet generator, or a photonic neural probe, that can be implanted into a living animal's brain.

The researchers used nanophotonic technology to create ultrathin silicon-based photonic neural probes that emit multiple addressable thin sheets of light with thicknesses <16 micrometers over propagation distances of 300 micrometers in free space. When tested in brain tissues from mice that were genetically engineered to express fluorescent proteins in their brains, the probes permitted the researchers to image areas as large as 240 ?m × 490 ?m. Moreover, the level of image contrast was superior to that with an alternative imaging method called epifluorescence microscopy.

Describing the significance of his team's work, the study's lead author, Wesley Sacher, says, "This new implantable photonic neural probe technology for generating light sheets within the brain circumvents many of the constraints that have limited the use of light-sheet fluorescence imaging in experimental neuroscience. We predict that this technology will lead to new variants of light-sheet microscopy for deep brain imaging and behavior experiments with freely moving animals."

Such variants would be a boon to neuroscientists seeking to understand the workings of the brain.

Source: ScienceDaily

Noninvasive technology steps ahead to help epilepsy patients

 Professor Bin He's team at Carnegie Mellon University, in collaboration with the Mayo Clinic, has discovered that fast oscillations in scalp-recorded electroencephalography can pinpoint brain tissues responsible for epileptic seizures. The collaborative research, recently published in the Proceedings of the National Academy of Sciences (PNAS), leverages noninvasive EEG technology along with the development of a novel machine learning algorithm to automatically identify and delineate concurrent high-frequency oscillations and epileptiform spikes, a key link related to epilepsy. In the near future, these findings may be harnessed to rethink imaging and treatment options for epilepsy patients.

More than 70 million people across the globe are affected by epilepsy, one of the most common neurological disorders. For people with epilepsy, brain activity becomes abnormal, causing seizures or unusual behavior, sensations, and sometimes loss of awareness. The incurable condition affects men and women of all ages, races, and ethnic backgrounds.

While medication is an effective treatment option for some, nearly one-third of epileptic patients do not respond well to medication. Many of these patients undergo surgical removal of the epileptic tissues to stop their seizures, if such epileptic foci can be identified in the brain and safely removed. The go-to clinical process to observe and localize epileptogenic brain activity, known as intracranial electroencephalography (iEEG), is invasive and involves drilling holes in the skull or removing a part of the skull, to place electrodes on the brain. Furthermore, iEEG recording is also time-consuming, lasting from days to weeks, until a spontaneous seizure occurs and can be monitored.

New groundbreaking research led by Bin He, professor of biomedical engineering at Carnegie Mellon University, in collaboration with the Mayo Clinic, combines clinical application and engineering innovation to present a safe, noninvasive, cost-effective, and quicker imaging option for patients with epilepsy.

Other researchers have attempted noninvasive EEG studies; however, He's work is unique in that it discovers and automatically records a novel link between high-frequency oscillations (HFOs) and epileptiform spikes. The link, in turn, identifies a unique biomarker by which the epileptogenic brain can be delineated and localized, thus offering extremely desirable means for noninvasive management of epilepsy, as well as aiding with treatment options.

"Over the years, HFOs have been identified as a promising biomarker for localizing epileptogenic brain tissues and potentially guiding neurosurgery correlated with the origin of seizures," explained He. "Challenges exist in that there are both physiological and pathological HFOs. Only pathological HFOs are tagged with epilepsy and helpful for clinical use, and unfortunately, differentiating between the two is highly-complicated using current practices and methods. Our team hypothesized and proved through morphological and source imaging evidence that pathological HFOs can be identified by the concurrence of HFOs and epileptiform spikes, all recorded noninvasively over the scalp."

He's collaborative study observed and recorded 25 patients with temporal epilepsy. Using a novel technology, the group was able to automatically identify the scalp recorded HFOs consistently cooccurring with epileptiform spikes and localize the corresponding cortical sources generating these events using source imaging techniques. In tandem, they also further validated the clinical value of using the identified pathological HFOs in determining the underlying epileptic tissues responsible for generating seizures, in comparison to clinical findings defined by epileptologists, and the surgical outcomes in the patients. He's results demonstrated significantly improved performance of the new method with comparison to the conventional spike imaging method.

Coming full circle, these findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable epileptic patients.

"This technology, if it advances to hospitals and medical centers, could be lifechanging," said He. "It is completely safe and noninvasive, and it occurs over a much shorter timeframe. It is a truly exciting development that brings with it significant societal and financial implications."

Looking ahead, the desire is to expand clinical studies and validate in more patients, with the eventual goal of having the technology adopted worldwide, across the healthcare industry.

This work was funded in part by the National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Institute of Mental Health, and National Center for Complementary and Integrative Health.

Other collaborators on the PNAS paper include the first author Zhengxiang Cai, a BME Ph.D. student in He's lab; Abbas Sohrabpour and Haiteng Jiang, BME postdoctoral associates; Shuai Ye, BME Ph.D. student; and clinical co-authors Gregory Worrell, Boney Joseph, and Benjamin Brinkmann of the Mayo Clinic.

Source: ScienceDaily

Fiber-optic ultrasonic imaging probe for future nanoscale disease diagnostics

 Scientists at the University of Nottingham have developed an ultrasonic imaging system, which can be deployed on the tip of a hair-thin optical fibre, and will be insertable into the human body to visualise cell abnormalities in 3D.

The new technology produces microscopic and nanoscopic resolution images that will one day help clinicians to examine cells inhabiting hard-to-reach parts of the body, such as the gastrointestinal tract, and offer more effective diagnoses for diseases ranging from gastric cancer to bacterial meningitis.

The high level of performance the technology delivers is currently only possible in state-of-the-art research labs with large, scientific instruments -- whereas this compact system has the potential to bring it into clinical settings to improve patient care.

The Engineering and Physical Sciences Research Council (EPSRC)-funded innovation also reduces the need for conventional fluorescent labels -- chemicals used to examine cell biology under a microscope -- which can be harmful to human cells in large doses.

The findings are being reported in a new paper, entitled 'Phonon imaging in 3D with a fibre probe' published in the Nature journal, Light: Science & Applications.

Paper author, Salvatore La Cavera, an EPSRC Doctoral Prize Fellow from the University of Nottingham Optics and Photonics Research Group, said of the ultrasonic imaging system: "We believe its ability to measure the stiffness of a specimen, its bio-compatibility, and its endoscopic-potential, all while accessing the nanoscale, are what set it apart. These features set the technology up for future measurements inside the body; towards the ultimate goal of minimally invasive point-of-care diagnostics."

Currently at prototype stage, the non-invasive imaging tool, described by the researchers as a "phonon probe," is capable of being inserted into a standard optical endoscope, which is a thin tube with a powerful light and camera at the end that is navigated into the body to find, analyse, and operate on cancerous lesions, among many other diseases. Combining optical and phonon technologies could be advantageous; speeding up the clinical workflow process and reducing the number of invasive test procedures for patients.

3D mapping capabilities

Just as a physician might conduct a physical examination to feel for abnormal 'stiffness' in tissue under the skin that could indicate tumours, the phonon probe will take this '3D mapping' concept to a cellular level.

By scanning the ultrasonic probe in space, it can reproduce a three-dimensional map of stiffness and spatial features of microscopic structures at, and below, the surface of a specimen (e.g. tissue); it does this with the power to image small objects like a large-scale microscope, and the contrast to differentiate objects like an ultrasonic probe.

"Techniques capable of measuring if a tumour cell is stiff have been realised with laboratory microscopes, but these powerful tools are cumbersome, immobile, and unadaptable to patient-facing clinical settings. Nanoscale ultrasonic technology in an endoscopic capacity is poised to make that leap," adds Salvatore La Cavera.

How it works

The new ultrasonic imaging system uses two lasers that emit short pulses of energy to stimulate and detect vibrations in a specimen. One of the laser pulses is absorbed by a layer of metal -- a nano-transducer (which works by converting energy from one form to another) -- fabricated on the tip of the fibre; a process which results in high-frequency phonons (sound particles) getting pumped into the specimen. Then a second laser pulse collides with the sound waves, a process known as Brillouin scattering. By detecting these "collided" laser pulses, the shape of the travelling sound wave can be recreated and displayed visually.

The detected sound wave encodes information about the stiffness of a material, and even its geometry. The Nottingham team was the first to demonstrate this dual-capability using pulsed lasers and optical fibres.

The power of an imaging device is typically measured by the smallest object that can be seen by the system, i.e. the resolution. In two dimensions the phonon probe can "resolve" objects on the order of 1 micrometre, similar to a microscope; but in the third dimension (height) it provides measurements on the scale of nanometres, which is unprecedented for a fibre-optic imaging system.

Future applications

In the paper, the researchers demonstrate that the technology is compatible with both a single optical fibre and the 10-20,000 fibres of an imaging bundle (1mm in diameter), as used in conventional endoscopes.

Consequently, superior spatial resolution and wide fields of view could routinely be achieved by collecting stiffness and spatial information from multiple different points on a sample, without needing to move the device -- bringing a new class of phonon endoscopes within reach.

Beyond clinical healthcare, fields such as precision manufacturing and metrology could use this high-resolution tool for surface inspections and material characterisation; a complementary or replacement measurement for existing scientific instruments. Burgeoning technologies such as 3D bio-printing and tissue engineering could also use the phonon probe as an inline inspection tool by integrating it directly to the outer diameter of the print-needle.

Next, the team will be developing a series of biological cell and tissue imaging applications in collaboration with the Nottingham Digestive Diseases Centre and the Institute of Biophysics, Imaging and Optical Science at the University of Nottingham; with the aim to create a viable clinical tool in the coming years.

Source: ScienceDaily

New nanoparticle design paves way for improved detection of tumors

 Nano-sized particles have been engineered in a new way to improve detection of tumors within the body and in biopsy tissue, a research team in Sweden reports. The advance could enable identifying early stage tumors with lower doses of radiation.

In order to enhance visual contrast of living tissues, state-of-the-art imaging relies on agents such as fluorescent dyes and biomolecules. Advances in nanoparticle research have expanded the array of promising contrast agents for more targeted diagnostics, and now a research team from KTH Royal Institute of Technology has raised the bar further yet. They are combining optical and X-ray fluorescence contrast agents into a single enhancer for both modes.

Muhammet Toprak, Professor of Materials Chemistry at KTH, says the synthesis of contrast agents introduces a new dimension in the field of X-ray bio-imaging. The research was reported in the American Chemical Society journal, ACS Nano.

"This unique design of nanoparticles paves the way for in vivo tumor diagnostics, using X-ray fluorescence computed tomography (XFCT)," Toprak says.

He says the new "core-shell nanoparticles" may have a role to play in the development of theranostics, a portmanteau for therapy and diagnostics, in which for example single drug-loaded particles could both detect and treat malignant tissues.

The core-shell contrast agent gets its name from its architecture: it consists of a core combination of nanoparticles with previously-established potential in X-ray fluorescence imaging, such as ruthenium and molybdenum (IV) oxide. This core is encased in a shell comprised of silica and Cy5.5, a near-infrared fluorescence-emitting dye for optical imaging techniques such as optical microscopy and spectroscopy.

Toprak says that encapsulating the Cy5.5 dye within the silica shell improves the agent's brightness and extends its photo-stability -- enabling the dual optical/X-Ray imaging approach. In addition, silica provides the benefit of tempering the toxic effects of the core nanoparticles.

Tests with laboratory mice have shown that the XFCT contrast agents enable location of early stage tumors of only a few millimetres in size.

Toprak says the technology opens the possibility to identify early stage tumors in living tissue. That's because the presence of multiple contrast agents increases the odds that diseased areas will show up in scans, even as the distribution of the nanoparticles becomes obscured by their interaction with proteins or other biological molecules.

"Nanoparticles of different size, originating from the same material, don't appear to be distributed in the blood in the same concentrations," Toprak says. "That's because when they come into contact with your body, they're quickly wrapped in various biological molecules -- which gives them a new identity."

A multitude of contrast agents for XFCT would enable studying the biodistribution of nanoparticles in-vivo using low-dose X-rays, he says. That would allow identifying the best size and surface chemistry of the nanoparticles for the desired targeting and imaging of the diseased region.

In addition to Toprak, the study was co-authored by Giovanni M. Saladino, Carmen Vogt, Yuyang Li, Kian Shaker, Bertha Brodin, Martin Svenda and Hans M. Hertz.

Source: ScienceDaily

Nuclear terrorism could be intercepted by neutron-gamma detector that pinpoints source

 Scanning technology aimed at detecting small amounts of nuclear materials was unveiled by scientists in Sweden today, with the hope of preventing acts of nuclear terrorism.

Bo Cederwall, a professor of physics at KTH Royal Institute of Technology, says the technology can be used in airports and seaports for routine inspection of passengers and goods. The research is published and featured in the journals Science Advances and Science, respectively.

A form of tomography, the system enables quick 3D imaging of the source of neutron and gamma ray emissions from weapons-grade plutonium and other special nuclear materials, Cederwall says.

The so-called Neutron-Gamma Emission Tomography (NGET) system goes beyond the capabilities of existing radiation portal monitors, by measuring the time and energy correlations between particles emitted in nuclear fission, and using machine learning algorithms to visualize where they're coming from. The system looks for coincidences of neutron and gamma ray emissions -- which when mapped together in real-time allow pinpointing their origin.

"The technology has a very high sensitivity and can within a few seconds detect gram-amounts of plutonium depending on the application and the plutonium isotope composition," Cederwall says. "It takes a little longer to get a really good picture so you can see exactly where the plutonium is. However, this can be done completely automatically."

But NGET isn't only for nuclear weapons and radiation-dispersing "dirty bombs" -- it can be used to detect environmental radiation too, such as leaks from nuclear facilities or even natural sources. Cederwall says the research group is looking into equipping drones with the NGET system for this purpose.

"In case of a radiological emergency, It is extremely important to be able to quickly map the radioactive contamination in the environment in order to protect the population in the best possible way," he says.

Source: ScienceDaily

Tiny, wireless, injectable chips use ultrasound to monitor body processes

 Widely used to monitor and map biological signals, to support and enhance physiological functions, and to treat diseases, implantable medical devices are transforming healthcare and improving the quality of life for millions of people. Researchers are increasingly interested in designing wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. These devices could be used to monitor physiological conditions, such as temperature, blood pressure, glucose, and respiration for both diagnostic and therapeutic procedures.

To date, conventional implanted electronics have been highly volume-inefficient -- they generally require multiple chips, packaging, wires, and external transducers, and batteries are often needed for energy storage. A constant trend in electronics has been tighter integration of electronic components, often moving more and more functions onto the integrated circuit itself.

Researchers at Columbia Engineering report that they have built what they say is the world's smallest single-chip system, consuming a total volume of less than 0.1 mm3. The system is as small as a dust mite and visible only under a microscope. In order to achieve this, the team used ultrasound to both power and communicate with the device wirelessly. The study was published online May 7 in Science Advances.

"We wanted to see how far we could push the limits on how small a functioning chip we could make," said the study's leader Ken Shepard, Lau Family professor of electrical engineering and professor of biomedical engineering. "This is a new idea of 'chip as system' -- this is a chip that alone, with nothing else, is a complete functioning electronic system. This should be revolutionary for developing wireless, miniaturized implantable medical devices that can sense different things, be used in clinical applications, and eventually approved for human use."

The team also included Elisa Konofagou, Robert and Margaret Hariri Professor of Biomedical engineering and professor of radiology, as well as Stephen A. Lee, PhD student in the Konofagou lab who assisted in the animal studies.

The design was done by doctoral student Chen Shi, who is the first author of the study. Shi's design is unique in its volumetric efficiency, the amount of function that is contained in a given amount of volume. Traditional RF communications links are not possible for a device this small because the wavelength of the electromagnetic wave is too large relative to the size of the device. Because the wavelengths for ultrasound are much smaller at a given frequency because the speed of sound is so much less than the speed of light, the team used ultrasound to both power and communicate with the device wirelessly. They fabricated the "antenna" for communicating and powering with ultrasound directly on top of the chip.

The chip, which is the entire implantable/injectable mote with no additional packaging, was fabricated at the Taiwan Semiconductor Manufacturing Company with additional process modifications performed in the Columbia Nano Initiative cleanroom and the City University of New York Advanced Science Research Center (ASRC) Nanofabrication Facility.

Shepard commented, "This is a nice example of 'more than Moore' technology -- we introduced new materials onto standard complementary metal-oxide-semiconductor to provide new function. In this case, we added piezoelectric materials directly onto the integrated circuit to transducer acoustic energy to electrical energy."

Konofagou added, "Ultrasound is continuing to grow in clinical importance as new tools and techniques become available. This work continues this trend."

The team's goal is to develop chips that can be injected into the body with a hypodermic needle and then communicate back out of the body using ultrasound, providing information about something they measure locally. The current devices measure body temperature, but there are many more possibilities the team is working on.

Source: ScienceDaily

Microscopic imaging without a microscope?

 The 30,000 or so genes making up the human genome contain the instructions vital to life. Yet each of our cells expresses only a subset of these genes in their daily functioning. The difference between a heart cell and a liver cell, for example, is determined by which genes are expressed -- and the correct expression of genes can mean the difference between health and disease.

Until recently, researchers investigating the genes underlying disease have been limited because traditional imaging techniques only allow for the study of a handful of genes at a time.

A new technique developed by Jun Hee Lee, Ph.D., and his team at the University of Michigan Medical School, part of Michigan Medicine, uses high-throughput sequencing, instead of a microscope, to obtain ultra-high-resolution images of gene expression from a tissue slide. The technology, which they call Seq-Scope, enables a researcher to see every gene expressed, as well single cells and structures within those cells, at incredibly high resolution: 0.6 micrometers or 66 times smaller than a human hair -- beating current methods by multiple orders of magnitude.

"Whenever a pathologist gets a tissue sample, they stain it and look at it under the microscope -- it's how they diagnose disease," explained Lee, an associate professor in the Department of Molecular & Integrative Physiology. "Instead of doing that, with our new method, we have made a microdevice that you can overlay with a tissue sample and sequence everything within it with a barcode with spatial coordinates."

Each so-called barcode is made up of a nucleotide sequence -- the pattern of A, T, G, an C -- found in DNA. Using these barcodes, a computer is able to locate every gene within a tissue sample, creating a Google-like database of all of the mRNAs transcribed from the genome.

"People have been trying to do this with other methods, such as microprinting, microbeads or microfluidic devices, but because of technological limitations, their resolution has been a distance of 20-100 micrometers. At that resolution you can't really see the level of detail needed to diagnose diseases," Lee said.

Lee adds that the technology has the potential to create an unbiased systematic way to analyze genes.

"Whenever we do science, we had to make a hypothesis about the role of two or three genes, but now we have genome-wide data at the microscopic scale and much more knowledge about what's going on inside that patient or model animal's tissue."

This knowledge could be used to provide insight into why certain patients respond to certain drugs while others do not, said Lee.

The team demonstrated the effectiveness of the technique using normal and diseased liver cells, successfully identifying dying liver cells, their surrounding inflamed immune cells and liver cells with altered gene expression.

"This technology actually showed many known pathological features that people have previously discovered but also many genes that are regulated in a novel way that was unrecognized previously," said Lee. "Seq-Scope technology, combined with other single cell RNA sequencing techniques, could accelerate scientific discoveries and might lead to a new paradigm in molecular diagnosis."

Source: ScienceDaily

Why does spaceflight impair the immune system?

 

• Since the Apollo missions started almost 60 years ago, scientists have been monitoring space travel’s negative effects on health.
• A new study concludes that reduced gravity makes the immune system malfunction, reducing the immune response.
• This study could pave the way for developing methods that reduce immune system impairment during long-term space exploration.

Dr. Millie Hughes-Fulford was one of the first female astronauts. Until her death in February 2021, she led a team of researchers at University of California, San Francisco (UCSF) and Stanford University in investigating the role of regulatory T cells (Tregs) in immune system dysfunction during space travel.

The lead author of the new study is Dr. Jordan Spatz, a postdoctoral fellow and space scientist at UCSF, and the senior author is Dr. Brice Gaudilliere, an associate professor in the Department of Anesthesia at the Stanford University School of Medicine.

The study appears in the latest edition of Scientific ReportsTrusted Source.

Alarming observations

Space scientists know that exposure to microgravity, or weak gravity, can wreak havoc on human health.

The Apollo astronauts experienced a number of illnesses upon their return to Earth. More than half of them caught colds or other infections within 1 week of completing their journeys.

Some astronauts dealt with inner ear disturbances, low blood pressure, arrhythmia, and reactivation of the chickenpox virus. Some also lost bone calciumTrusted Source or were dehydrated.

These findings inspired probes into the effects of microgravity on the immune system.

Over the past 6 decades, scientists have led such inquiries during rocket launches, shuttle trips, space station terms, and earthbound laboratory space gravity simulations.

Tregs turn rogue in space

Tregs play a vital role in regulating many types of immune responses. Often, these cells dampen the immune responses as an infection subsides.

They are involved in a number of processes, including oral toleranceTrusted Source, which is “the active process by which the immune system does not respond to an orally administered antigen,” such as food. Tregs also play a role in resistance to infections, allergy sensitivities, immune memory, and transplantation toleranceTrusted Source, in which the immune system does not attack transplanted tissue.

The current study’s findings indicate that space travel activates Tregs earlier, thereby damping down the immune system before the threat has been cleared.

Unexpected results

The scientists exposed blood samples from eight healthy adult participants to simulated microgravity.

They loaded the samples into a machine developed by the National Aeronautics and Space Administration (NASA), called the Rotating Wall Vessel, exposing the samples to 18 hours of either 1-gravity, which is the amount of gravity experienced on Earth, or microgravity.

Using a novel single-cell analysis, the researchers could pinpoint individual immune cells by type in order to detect and tally proteins involved in immune function.

This study offers greater insight into the cellular interactions that explain microgravity’s immunosuppressive effects.

According to the researchers, the lack of gravity seems to set off a multicellular response that may lower resistance to pathogens.

Surprisingly, when the team stimulated an immune response in the blood samples with two molecules that mimicked a pathogen, the Tregs dampened the resulting immune response before it had time to respond to the threat.

The study authors report: “Our data indicate that exposure to [microgravity] results in the broad inhibition of immune cell capacity to respond to a potent activating stimulus […] and are consistent with transcriptomic previous analyses of human immune cells exposed to the spaceflight environment.”

Dr. Gaudilliere calls this a “double whammy” of “a dampening of T lymphocyte immune activation responses — but also an exacerbation of immunosuppressive responses by Tregs.” T lymphocytes, which are also called T cells, play a central role in the body’s response to pathogens. Under microgravity, T cells are less responsive. However, antibody-producing B cells were not affected in the same way.

Certain limitations

The study’s authors mention several limitations. They stress that using a microgravity simulation model makes it hard to generalize the findings. However, they argue that this cost-effective experimentation can identify novel biological effects that can later be tested in-flight.

Also, the study’s design concentrated on one time point of exposure to low gravity. The team feels that future investigations with additional time points “are warranted and should be high priority.”

In addition, the short-term incubation time did not provide enough opportunity to measure differences in cell proliferation.

The evaluation also noted the immune response to a single stimulus, limiting the analysis of the functional response of immune cells to other stimuli or pathogens.

Implications

Reduced immune response, accelerated pathogen activity, and heightened viral shedding in astronauts in space pose significant risks for both short- and long-term space travel.

Dr. Spatz expresses concern about the growing public demand for space travel, as well:

“Early in the space program, most astronauts were young and extremely healthy, but now they tend to have much more training and are older. In addition, […] with the commercialization of spaceflight, there will be many older and less healthy individuals experiencing microgravity.”

The lead and senior study authors believe that their team’s work can aid in developing interventions to reduce the consequences of suppressed immunity during spaceflight.

Source: Medical News Today