Day: February 19, 2021

Gut Microbiome Changes are Linked to Ageing and Longevity

Ageing in humans is marked by compositional changes in the gut microbiome that become more unique later in life.

Researchers from the Institute for Systems Biology (ISB) analysed gut microbiome, phenotypic and clinical data from over 9000 people across three independent cohorts. Health and survival outcomes were tracked from longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old).

The researchers found that, starting in mid-to-late adulthood, gut microbiomes became increasingly unique as individuals aged, corresponding with a steady decline in the abundance of core bacterial genera common across humans.

Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. Gut microbiome uniqueness was highly correlated with several microbially-derived metabolites in blood plasma. One of them, tryptophan-derived indole, has been shown to extend lifespan in mice. Another metabolite, phenylacetylglutamine, showed the strongest association with uniqueness, and is known to be highly elevated in the blood of people over 100.

“This uniqueness signature can predict patient survival in the latest decades of life,” said study leader Dr Tomasz Wilmanski, who led the study. Healthy individuals aged around 80 showed continued microbial drift toward a uniqueness, but this drift was not seen in less healthy individuals of the same age.

“Interestingly, this uniqueness pattern appears to start in mid-life—40-50 years old—and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” Wilmanski said. Indoles are known to reduce inflammation in the gut, for example, and chronic inflammation is believed to drive age-related morbidities.

“Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health,” said co-corresponding author, microbiome specialist Dr Sean Gibbons. “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: (1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and (2) the maintenance of core microbes in less healthy individuals.”

This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood.

Source: Medical Xpress

Journal information: Gut microbiome pattern reflects healthy ageing and predicts survival in humans, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00348-0

NASA Awards Grant for Bone Loss Research

The US space agency NASA has awarded a US$750 000 grant to conduct research into how bone weakening in the absence of mechanical loading, as in zero gravity, can be reduced.

Dr Meghan E McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia, the recipient of the grant, will use the money to better understand how bone loss occurs in space from lack of gravity and also from disuse here on Earth.

“It’s a problem for the astronauts who are on the International Space Station for long periods of time, and it’s going to continue to be a problem for eventually trying to send astronauts to Mars,” Dr McGee-Lawrence said. It is also a problem in patients with spinal cord injuries, undergoing prolonged bedrest or physical inactivity.

“If we can find a way to make bone more sensitive to mechanical loading, then we would be able to increase bone mass with less effort. That is a long-term goal,” she says.

Her focus is the natural sensors of mechanical loading on the bone called osteocytes, and her lab found that tears, called plasma membrane disruptions, occur in osteocytes from mechanical loading, resulting in repair. They showed that these disruptions from loads happen in under a minute, and set off changes like letting in extra calcium, influencing osteoblast and osteoclast activity. If there are few tears from mechanical loading, osteoblasts are not needed and so osteoclasts will resorb some bone matrix. Even walking around has been shown to cause plasma membrane disruptions, something not possible for bedrest patients or astronauts in space.

With this in mind she posed the question, “can we do anything to reverse those processes. Can we do something to the osteocytes to make them either more likely to experience tears or more likely to repair those tears and then, accordingly, make it so there is less bone loss during disuse.”

Fewer tears seem to be not good, and she and her team want to further investigate what happens to the repair rate with disuse. They also want to know the best healing rate; slow for better osteocyte survival, or does osteocyte survival enable faster repair?

“The good news is we can dial it in either direction,” she says. However, they believe faster repair is not better because the calcium influx is linked to the cell’s response.

“Think of a membrane disruption as a doorway into the cell. If you slam the door too quickly, then there is not enough time for the cell to sense that tear and initiate the signaling to respond,” she explained.

She believes that proteins involved in repairing membrane tears, like PRKD1, are logical targets for genetic and pharmacological methods to either increase tears or speed up repair.

“The ultimate goal is can we come up with a way, whether it’s a drug therapy or a different type of regimen that can make these processes work better in astronauts and people on earth who are subjected to disuse as well,” she said.

Even with resistive exercises, astronauts lose bone mass in space. Bisphosphonates are only really effective with age-related bone loss and not loss from inactivity or lack of gravity. With the current most advanced exercise device on the International Space Station, astronauts come back to Earth fitter than when they left but still lose some bone mass. On a three-year voyage to Mars, many astronauts could return with osteoporosis. “That is really a problem. Not only are they losing bone actively while they are in space, at some point they have to come back to gravity… and then what happens?” she says. Recovering bone strength on Earth is a long and difficult process for astronauts. She and her research team are also finding that osteocytes are less likely to repair and survive tears after a long period of disuse.

There are effective therapies, like bisphosphonates, that can help age-related bone loss, but they have not been shown to be effective when disuse is the primary driver. “That is why we need to come up with better targets, more effective targets, to try to prevent disuse-induced bone loss,” she said. While it has long been clear that mechanical load also translates to stronger bones, just how remains a question, she says. She suspects the plasma membrane tears are key.

“We think the formation of these tears is important for how the bone cells know they are being exposed to that level of loading,” she said, with high-impact loading from running and jumping being particularly important. “Cells need a way to know what is going on outside their cell membrane. This is one way to do that.”

Source: News-Medical.Net

Confusion Results in Vaccine Priority for ‘6.2cm’ Tall UK Man

As a result of an error at his GP surgery, a healthy man aged 32 was offered an early COVID vaccination because his height was recorded as 6.2cm – giving him a calculated Body Mass Index (BMI) of 28 000.

Liam Thorp, political editor at The Liverpool Echo’s, said he was left “really confused” after he was offered the vaccine ahead of the government’s rollout, sharing the “frankly surreal” experience in a Twitter thread.  Vaccinations are not expected to begin until later in the year for the UK’s under-50s without underlying health conditions, perhaps as soon as March.

Manchester Evening News politics and investigations editor, Jennifer Williams, replied: “Should they not have been in touch before to see how the man the size of a thumb was getting on?” And palliative care doctor Rachel Clarke said: “This, for me, is the single best tweet of the entire pandemic, Liam. And may I please commend your decency in not exploiting your remarkable BMI to jump the queue?”

Despite being “on the chunky side”, Thorp didn’t think of his himself as obese. He said he was “uneasy”, thinking that he still ought to accept the invitation for vaccination, he contacted his GP about the situation whereupon he learned of the error which resulted in his height being recorded as 6.2cm – a mixup of his height as 6ft 2in (188cm). This resulted in his bizarre BMI of 28 000.

“If I had been less stunned, I would have asked why no one was more concerned that a man of these remarkable dimensions was slithering around south Liverpool. But he was very apologetic and really nice and I think he was just relieved that I found it so funny,” recalled Thorp.

Dr Fiona Lemmens, chair of NHS Liverpool clinical commissioning group, said: “I can see the funny side of this story but also recognise there is an important issue for us to address.”

Source: The Guardian

Dialysis Crisis from Texas Ice Storm

Widespread power outages and water supply issues have created a dialysis crisis in Texas, following an onslaught of snow, ice, and sub-freezing temperatures.

“To say we’re stressed is an understatement. Almost all outpatient dialysis units closed due to power outages. Trying desperately to do as many as we can inpatient. To make matters worse some of our hospitals lost water today (so no HD [haemodialysis]). Truly a nightmare,” tweeted Tessa Novick, MD, a nephrologist at the University of Texas at Austin.
Half of Texas’ dialysis centres, serving 54 000 people, were unable to operate in the wake of the severe ice storm that has caused widespread damage in Texas and other parts of the US. Some patients had been without dialysis for four to five days, causing risk of potentially life-threatening potassium and fluid problems.

The large storm system, unofficially called Winter Storm Uri, dropped snow and ice over Texas on February 14 and 15, resulting in widespread power failures as lines were damaged. Few clinics have generators. Water pipes have also frozen, and this is a further problem as dialysis needs clean water to prepare concentrates and dialysate, and to reprocess the machines for following patients.

Fresenius Kidney Care said that around half of its Houston area centres have been impacted by a lack of water, “with the other centres either fully operational or operating on generators.” Water truck deliveries will allow other centres to reopen.

Tiffany Jones-Smith, CEO of the Texas Kidney Foundation, pointed out that there were some bright spots, such as eight clinics in San Antonio that brought water in and have been day and night to dialyse patients from any closed clinic regardless of affiliation. Other clinics were following suit, and Jones-Smith said patients were being given Uber and Lyft coupons to reach their dialysis centres. “We’re just kind of banding together and figuring out what needs to be done,” she said.

Looking ahead to when the crisis had cleared, Jones-Smith said, “We can’t let this go, because we need to be prepared for the next time, not just reacting to chaos, which is what we’re doing right now. … There’s no getting around we’ve had an epic failure.”

Climate change is predicted to increase the frequency and severity of such extreme events in the future, requiring better preparation.

Source: MedPage Today

COVID in Zambia More Widespread Than Believed

A new study from Zambia has found almost a fifth of recently-deceased people in mid-2020 tested positive for COVID. 

The study, from the Boston University School of Public Health (BUSPH) study in Zambia, upends the notion that Africa somehow ‘dodged’ the worst of the COVID pandemic. Rather, the low reported rates are merely reflective of a lack of testing ability.

“Our findings cast doubt on the assumption that COVID-19 somehow skipped Africa or has not impacted the continent as heavily,” said study co-author Dr Lawrence Mwananyanda, a BUSPH adjunct research assistant professor of global health based in Lusaka. “This study shows that with proper diagnostics and testing, we can begin to identify the scale of COVID-19 in African countries such as Zambia. I hope this study will encourage African governments to look closer at the rollout of COVID-19 testing, as well as empower Africans to take proactive steps–such as wearing masks, physically distancing, and skipping handshakes–to protect themselves from COVID-19.”

The findings have important implications for global policy makers, who will need to ensure access to vaccines worldwide, along with monitoring.

The University Teaching Hospital morgue sees roughly 80% of people who die in Lusaka pass through it. From June to September, polymerase chain reaction tests detected COVID in 70 out of 364 recently-deceased people. A peak of 31% positive results was observed in July. Unlike the typical pattern of COVID deaths elsewhere, most of the deceased people who tested positive in this study were under 60 years old, including seven children. Given how rare paediatric COVID deaths are elsewhere, this is surprising, the researchers noted.

The researchers sought information about the symptoms of the 70 who tested positive. “In nearly all cases where we had those data, we found typical symptoms for COVID-19, yet only 6 had been tested before death,” Gill said. Of 75% of deaths outside hospital, none had been tested.

Monitoring COVID is not a simple task, especially in a country with limited resources. Zambia’s Ministry of Health has been very proactive and supportive of this and other COVID studies, the researchers said.

“They’re really grateful that we can provide them this data, and they can make informed decisions moving forward with this epidemic,” said Dr Mwananyanda.

The researchers were well-positioned to track COVID in Zambia, having conducted the ongoing Zambia Pertussis/RSV Infant Mortality Estimation Study (ZPRIME) at the morgue.

“Building studies such as this from scratch can take time and resources that can be difficult in the time needed to tackle the COVID-19 pandemic. We invested a lot of time and money and human resources to building infrastructure that allowed for that extensive surveillance,” said co-author Rachel Pieciak, a research fellow at BUSPH. “So, what we’ve done was repurpose ZPRIME study capacity to focus on enrolling all deaths across all ages and testing for COVID-19.”

The researchers expressed hope that similar studies could be repurposed for the COVID fight.

Source: News-Medical.Net

Journal information: Mwananyanda, L., et al. (2021) Covid-19 deaths in Africa: prospective systematic postmortem surveillance study. BMJ.

Novel Magnetic Technique Detects Malaria in Blood

A new magnetic method has been developed that can detect malaria, leading to faster, accurate and cheap diagnosis of the deadly disease.

An international study field-tested this new tool in Papua New-Guinea, in the hopes of helping the fight against this disease, which had 229 million reported cases in 2019, with 700 000 deaths a year.

“Malaria is easily treated but it is actually hard to diagnose, and because of that there can be over-treatment, which we have seen can lead to the spread of drug-resistant malaria,” said Dr Stephan Karl, a Senior Research Fellow in Malaria and Vector Biology at James Cook University’s Australian Institute of Tropical Health and Medicine.

“Improving malaria diagnosis, especially through the development of practical methods for resource-limited places, is important and timely,” he said.

An international team including the University of Augsburg’s Professor Istvan Kezsmarki, with the PNG Institute of Medical Research and the Burnet Institute, came up with the magnetic detection method, called rotating-crystal magneto-optical detection (RMOD).

When malaria parasites break down blood, the haeme molecules are aggregated by the parasites into biocrystals called haemezoin, which contain magnetic iron. This iron can is detectable by the RMOD method.

“I’ve studied the magnetic properties of malaria infected blood since 2006, and we engaged with Professor Kezsmarki’s team in 2013 to demonstrate the sensitivity of this test using human malaria parasites,” Dr Karl said.

A field study was successfully conducted, involving almost 1000 suspected malaria patients in a high-transmission area of Papua New-Guinea.

“After years of in-lab optimisation of the device, in collaboration with Dr. Karl we demonstrated the great potential of RMOD in fast and reliable malaria field tests performed in Papua New-Guinea,” Prof Kezsmarki said.

“We showed that RMOD performs well in comparison to the most reliable existing method..It’s very promising, as RMOD testing can be conducted after a short training session and provides test results within 10 minutes. From a funding perspective the cost is very low since no expensive reagents are used,” said Dr Karl.

Dr Karl said the aim was to refine the design until a test could be done by a simple button push.

Source: Medical Xpress

Journal information: L. Arndt et al, Magneto-optical diagnosis of symptomatic malaria in Papua New Guinea, Nature Communications (2021). DOI: 10.1038/s41467-021-21110-w