An infection with the human immunodeficiency virus (HIV) was previously considered incurable. The reason for this is that the virus “sleeps” in the genome of infected cells for long periods of time, making it invisible and inaccessible to both the immune system and antiviral drugs. The “Düsseldorf patient,” a 53-year-old man, is now the third person in the world to be completely cured of the HI virus by a stem cell transplant.

The patient, treated at the University Hospital Düsseldorf for his HIV infection, had received a stem cell transplant due to a blood cancer. As in the cases of the first two patients named “Berlin” and “London,” the Düsseldorf patient received stem cells from a healthy donor whose genome contains a mutation in the gene for the HIV-1 co-receptor CCR5. This mutation makes it impossible for most HI viruses to enter human CD4+ T-lymphocytes, their major target cells.

Following transplantation, the patient was carefully monitored virologically and immunologically for almost ten years. Using a variety of sensitive techniques, the researchers analysed the patient’s blood and tissue samples to closely monitor immune responses to HIV and the continued presence or even replication of the virus. Already shortly after transplantation and over the entire course of the study years, neither replicating virus nor antibodies or reactive immune cells against HIV were detected. More than four years ago, the antiviral therapy against HIV was discontinued. Ten years after transplantation and four years after the end of anti-HIV therapy, the Düsseldorf patient could be declared cured by the international research consortium.

“This case of curing a chronic HIV infection by stem cell transplantation shows that HIV can in principle be cured,” says Prof. Julian Schulze zur Wiesch, DZIF scientist at the University Medical Center Hamburg-Eppendorf and one of the study leads. “In particular, the results of this study are also enormously important for further research into a cure for HIV for the vast majority of people living with HIV for whom stem cell transplantation is not an option.”

“This method we developed allows us to easily create very large bulk samples within several minutes, rather than days or weeks using traditional methods,” said Luyao Zheng, a postdoctoral researcher in the Department of Materials Science at Penn State and lead author on the study. “And our materials are high quality — their properties can compete with single-crystal perovskites.”

The researchers used a sintering method called the electrical and mechanical field-assisted sintering technique (EM-FAST) to create the devices. Sintering is a commonly used process to compress fine powders into a solid mass of material using heat and pressure.

A typical process for making perovskites involves wet chemistry — the materials are liquefied in a solvent solution and then solidified into thin films. These materials have excellent properties, but the approach is expensive and inefficient for creating large perovskites and the solvents used may be toxic, the scientists said.

“Our technique is the best of both worlds,” said Bed Poudel, a researcher professor at Penn State and a co-author. “We get single-crystal-like properties, and we don’t have to worry about size limitations or any contamination or yield of toxic materials.”

Because it uses dry materials, the EM-FAST technique opens the door to include new dopants, ingredients added to tailor device properties, that are not compatible with the wet chemistry used to make thin films, potentially accelerating the discovery of new materials, the scientists said.

“This opens up possibilities to design and develop new classes of materials, including better thermoelectric and solar materials, as well as X- and γ-ray detectors,” said Amin Nozariasbmarz, assistant research professor at Penn State and a co-author. “Some of the applications are things we already know, but because this is a new technique to make new halide perovskite materials with controlled properties, structures, and compositions, maybe there is room in the future for new breakthroughs to come from that.”

In addition, the new process allows for layered materials — one powder underneath another — to create designer compositions. In the future, manufactures could design specific devices and then directly print them from dry powders, the scientists said.

“We anticipate this FAST perovskite would open another dimension for high throughput material synthesis, future manufacturing directly printing devices from powder and accelerating the material discovery of new perovskite compositions,” said Kai Wang, an assistant research professor at Penn State and a co-author.

EM-FAST, also known as spark plasma sintering, involves applying electric current and pressure to powders to create new materials. The process has a 100% yield — all the raw ingredients go into the final device, as opposed to 20 to 30% in solution-based processing.

The technique produced perovskite materials at .2 inch per minute, allowing scientists to create quickly create large devices that maintained high performance in laboratory tests. The team reported their findings in the journal Nature Communications.

Penn State scientists have long used EM-FAST to create thermoelectric devices. This work represents the first attempt to create perovskite materials with the technique, the scientists said.

“Because of the background we have, we were talking and thought we could change some parameters and try this with perovskites,” Nozariasbmarz said. “And it just opened a door to a new world. This paper is a link to that door — to new materials and new properties.”

Other Penn State researchers on the project were Wenjie Li and Dong Yang, assistant research professors; Ke Wang, staff scientist in the Materials Research Institute; Jungjin Yoon, Tao Ye and Yu Zhang, postdoctoral researchers; Yuchen Hou, doctoral candidate; and Shashank Priya, former associate vice president for research and director of strategic initiatives and professor of materials science and engineering.

Also contributing was Mohan Sanghadasa, U.S. Army Combat Capabilities Development Command Aviation and Missile Center.

Researchers received support from the National Science Foundation Industry-University Research Partnerships’ Center for Energy Harvesting Materials and Systems, U.S. Department of Energy’s Office of Energy Efficiency and Renewable Energy, Air Force Office of Scientific Research, and Office of Naval Research and Army Research.

The findings, published Feb. 9 in the journal Population Studies, counter prevailing wisdom that excess weight boosts mortality risk only in extreme cases.

The statistical analysis of nearly 18,000 people also shines a light on the pitfalls of using body mass index (BMI) to study health outcomes, providing evidence that the go-to metric can potentially bias findings. After accounting for those biases, it estimates that about 1 in 6 U.S. deaths are related to excess weight or obesity.

“Existing studies have likely underestimated the mortality consequences of living in a country where cheap, unhealthy food has grown increasingly accessible, and sedentary lifestyles have become the norm,” said author Ryan Masters, associate professor of sociology at CU Boulder.

“This study and others are beginning to expose the true toll of this public health crisis.”

Challenging the obesity paradox

While numerous studies show that heart disease, high blood pressure and diabetes (which are often associated with being overweight) elevate mortality risk, very few have shown that groups with higher BMIs have higher mortality rates.

Instead, in what some call the “obesity paradox,” most studies show a U-shaped curve: Those in the “overweight” category (BMI 25-30) surprisingly have the lowest mortality risk. Those in the “obese” category (30-35) have little or no increased risk over the so-called “healthy” category (18.5-25). And both the “underweight” (less than 18.5) and extremely obese (35 and higher) are at increased risk of death.

“The conventional wisdom is that elevated BMI generally does not raise mortality risk until you get to very high levels, and that there are actually some survival benefits to being overweight,” said Masters, a social demographer who has spent his career studying mortality trends. “I have been suspicious of these claims.”

He noted that BMI, which doctors and scientists often use as a health measure, is based on weight and height only and doesn’t account for differences in body composition or how long a person has been overweight.

“It’s a reflection of stature at a point in time. That’s it,” said Masters, noting that Tom Cruise (at 5 feet 7 inches and an extremely muscular 201 pounds at one point), had a BMI of 31.5, famously putting him in the category of “obese.” “It isn’t fully capturing all of the nuances and different sizes and shapes the body comes in.”

To see what happened when those nuances were considered, Masters mined the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2015, looking at data from 17,784 people, including 4,468 deaths.

He discovered that a full 20% of the sample characterized as “healthy” weight had been in the overweight or obese category in the decade prior. When set apart, this group had a substantially worse health profile than those in the category whose weight had been stable.

Masters pointed out that a lifetime carrying excess weight can lead to illnesses that, paradoxically, lead to rapid weight loss. If BMI data is captured during this time, it can skew study results.

“I would argue that we have been artificially inflating the mortality risk in the low-BMI category by including those who had been high BMI and had just lost weight recently,” he said.

Meanwhile, 37% of those characterized as overweight and 60% of those with obese BMI had been at lower BMIs in the decade prior. Notably, those who had only recently gained weight had better health profiles.

“The health and mortality consequences of high BMI are not like a light switch,” said Masters. “There’s an expanding body of work suggesting that the consequences are duration-dependent.”

By including people who had spent most of their life at low-BMI weight in the high-BMI categories, previous studies have inadvertently made high BMI look less risky than it is, he said.

When he looked at differences in fat distribution within BMI categories, he also found that variations made a huge difference in reported health outcomes.

Exposing a public health problem

Collectively, the findings confirm that studies have been “significantly affected” by BMI-related bias.

When re-crunching the numbers without these biases, he found not a U-shape but a straight upward line, with those with low BMI (18.5-22.5) having the lowest mortality risk.

Contrary to previous research, the study found no significant mortality risk increases for the “underweight” category.

While previous research estimated 2 to 3% of U.S. adult deaths were due to high BMI, his study pegs the toll at eight times that.

Masters said he hopes the research will alert scientists to be “extremely cautious” when making conclusions based on BMI. But he also hopes the work will draw attention to what he sees not as a problem for individuals alone to solve but rather a public health crisis fueled by an unhealthy or “obesogenic” environment in the U.S.

“For groups born in the 1970s or 1980s who have lived their whole lives in this obesogenic environment, the prospects of healthy aging into older adulthood does not look good right now,” he said. “I hope this work can influence higher-level discussions about what we as a society can do about it.”

This problem was tackled in a multidisciplinary project led by Prashant Mehta and Mattia Gazzola, professors of mechanical science & engineering at the University of Illinois Urbana-Champaign. As reported in Proceedings of the Royal Society A, the two researchers and their groups have developed a physiologically accurate model of octopus arm muscles. “Our model, the first of its kind, not only provides insight into the biological problem, but a framework for design and control of soft robots going forward,” Mehta said.

The impressive capabilities of octopus arms have long served as an inspiration for the design and control of soft robots. Such soft robots have the potential to perform complex tasks in unstructured environments while operating safely around humans, with applications ranging from agriculture to surgery.

Graduate student Heng-Sheng Chang, the study’s lead author, explained that soft-bodied systems like octopuses’ arms present a major modeling and control challenge. “They are driven by three major internal muscle groups — longitudinal, transverse, and oblique — that cause the arm to deform in several modes — shearing, extending, bending, and twisting,” he said. “This endows the soft muscular arms with significant freedom, unlike their rigid counterparts.”

The team’s key insight was to express the arm musculature using a stored energy function, a concept borrowed from the theory of continuum mechanics. Postdoctoral scholar and corresponding author Udit Halder explained that “The arm rests at the minimum of an energy landscape. Muscle actuations modify the stored energy function, thus shifting the equilibrium position of the arm and guiding the motion.”

Interpreting the muscles using stored energy dramatically simplifies the arm’s control design. In particular, the study outlines an energy-shaping control methodology to compute the necessary muscle activations for solving manipulation tasks such as reaching and grasping. When this approach was numerically demonstrated in the software environment Elastica, This model led to remarkably life-like motion when an octopus arm was simulated in three dimensions. Moreover, according to Halder, “Our work offers mathematical guarantees of performance that are often lacking in alternative approaches, including machine learning.”

“Our work is part of a larger ecosystem of ongoing collaborations at the University of Illinois,” Mehta said. “Upstream, there are biologists who perform experiments on octopuses. Downstream, there are roboticists who are taking these mathematical ideas and applying them to real soft robots.”

Mehta’s and Gazzola’s groups collaborated with Rhanor Gillette, Illinois Professor Emeritus of molecular and integrative physiology, to incorporate observed octopus physiology into their mathematical model for this study. Future work will discuss the biological implications of energy-based control. In addition, the researchers are collaborating with Girish Krishnan, an Illinois professor of industrial & enterprise systems engineering, to incorporate their mathematical ideas into real soft robot design and control. This will not only create a systematic way of controlling soft robots, but will also provide a deeper understanding of their working mechanisms.

This work was part of the CyberOctopus project, a multidisciplinary university research initiative in the University of Illinois’ Coordinated Science Laboratory supported by the Office of Naval Research.

Now, having examined the evolution of X7 using 20 years of data gathered by the Galactic Center Orbit Inintiative, astronomers from the UCLA Galactic Center Group and the Keck Observatory propose that it could be a cloud of dust and gas that was ejected during the collision of two stars.

Over time, they report, X7 has stretched, and it is being pulled apart as the black hole drags it closer, exerting its tidal force upon the cloud. They expect that within the next few decades, X7 will disintegrate and the gas and dust of which it is composed will eventually be drawn toward the black hole, which is called Sagittarius A*, or Sgr A*.

The study is published in The Astrophysical Journal.

“No other object in this region has shown such an extreme evolution,” said Anna Ciurlo, a UCLA assistant researcher and the paper’s lead author. “It started off comet-shaped and people thought maybe it got that shape from stellar winds or jets of particles from the black hole. But as we followed it for 20 years we saw it becoming more elongated. Something must have put this cloud on its particular path with its particular orientation.”

X7 has a mass of about 50 Earths and is on an orbital path around Sgr A* that would take 170 years to complete.

But that might never happen. Based on its trajectory, the team estimates that X7 will make its closest approach to Sgr A* around the year 2036, and then likely spiral toward Sgr A* and disappear.

“We anticipate the strong tidal forces exerted by the galactic black hole will ultimately tear X7 apart before it completes even one orbit,” said co-author Mark Morris, UCLA professor of physics and astronomy.

Tidal forces are the gravitational pull that cause an object approaching a black hole to stretch; the side of the object closest to the black hole is pulled much more strongly than the opposite end.

X7 shows some of the same properties as the other strange dusty objects orbiting Sgr A*. Those so-called G objects look like gas but behave like stars. But X7’s shape and velocity have changed more dramatically than G objects’ have. As it accelerates toward the black hole, X7 is moving rapidly, clocking in at speeds of up to around 700 miles per second.

“It’s exciting to see significant changes of X7’s shape and dynamics in such great detail over a relatively short time scale as the gravitational forces of the supermassive black hole at the center of the Milky Way influences this object,” Randy Campbell, a co-author of the paper and the science operations lead at the Keck Observatory, said in a statement.

Although X7’s origin is still the subject of debate, the finding suggests that it arose after two stars collided.

“One possibility is that X7’s gas and dust were ejected at the moment when two stars merged,” Ciurlo said. “In this process, the merged star is hidden inside a shell of dust and gas, which might fit the description of the G objects. And the ejected gas perhaps produced X7-like objects.”

The merger of two stars is very common, especially when they are near black holes, Ciurlo said.

“This is a very messy process: The stars circle each other, get closer, merge, and the new star is hidden within a cloud of dust and gas,” she said. “X7 could be the dust and gas ejected from a merged star that’s still out there somewhere.”

The findings are the first estimate of X7’s mildly elliptical orbit and the most robust analysis to date of the remarkable changes to its appearance, shape and behavior. The research team will continue to use the Keck Observatory to monitor X7’s dramatic changes as the power of the black hole’s gravity yanks it apart.

“It’s a privilege to be able to study the extreme environment at the center of our galaxy,” Campbell said in the statement. “This study can only be done using Keck’s superb capabilities, and performed at the very special and revered Maunakea, with honor and respect to the mauna.”

Using observations taken with the Atacama Large Millimeter Array (ALMA), a radio observatory sited in Chile, the team have determined that the galaxy, named COS-87259, containing this new supermassive black hole is very extreme, forming stars at a rate 1000 times that of our own Milky Way and containing over a billion solar masses worth of interstellar dust. The galaxy shines bright from both this intense burst of star formation and the growing supermassive black hole at its centre.

The black hole is considered to be a new type of primordial black hole — one heavily enshrouded by cosmic “dust,” causing nearly all of its light to be emitted in the mid-infrared range of the electromagnetic spectrum. The researchers have also found that this growing supermassive black hole (frequently referred to as an active galactic nucleus) is generating a strong jet of material moving at near light speed through the host galaxy.

Today, black holes with masses millions to billions of times greater than that of our own Sun sit at the centre of nearly every galaxy. How these supermassive black holes first formed remains a mystery for scientists, particularly because several of these objects have been found when the Universe was very young. Because the light from these sources takes so long to reach us, we see them as they existed in the past; in this case, just 750 million years after the Big Bang, which is approximately 5% of the current age of the Universe.

What is particularly astonishing about this new object is that it was identified over a relatively small patch of the sky typically used to detect similar objects — less than 10 times the size of the full moon — suggesting there could be thousands of similar sources in the very early Universe. This was completely unexpected from previous data.

The only other class of supermassive black holes we knew about in the very early Universe are quasars, which are active black holes that are relatively unobscured by cosmic dust. These quasars are extremely rare at distances similar to COS-87259, with only a few tens located over the full sky. The surprising discovery of COS-87259 and its black hole raises several questions about the abundance of very early supermassive black holes, as well as the types of galaxies in which they typically form.

Ryan Endsley, the lead author of the paper and now a Postdoctoral Fellow at The University of Texas at Austin, says “These results suggest that very early supermassive black holes were often heavily obscured by dust, perhaps as a consequence of the intense star formation activity in their host galaxies. This is something others have been predicting for a few years now, and it’s really nice to see the first direct observational evidence supporting this scenario.”

Similar types of objects have been found in the more local, present-day Universe, such as Arp 299 shown here. In this system, two galaxies are crashing together generating an intense starburst as well as heavy obscuration of the growing supermassive black hole in one of the two galaxies.

Endsley adds, “While nobody expected to find this kind of object in the very early Universe, its discovery takes a step towards building a much better understanding of how billion solar mass black holes were able to form so early on in the lifetime of the Universe, as well how the most massive galaxies first evolved.”

“We saw a clear dose-response relationship, so the more beneficial factors someone has in terms of having higher quality of sleep, they also have a stepwise lowering of all cause and cardiovascular mortality,” said Frank Qian, MD, an internal medicine resident physician at Beth Israel Deaconess

Medical Center, clinical fellow in medicine at Harvard Medical School and co-author of the study. “I think these findings emphasize that just getting enough hours of sleep isn’t sufficient. You really have to have restful sleep and not have much trouble falling and staying asleep.”

For their analysis, Qian and team included data from 172,321 people (average age 50 and 54% women) who participated in the National Health Interview Survey between 2013 and 2018. This survey is fielded each year by the Centers for Disease Control and Prevention (CDC) and the National Center for Health Statistics to help gauge the health of the U.S. population and includes questions about sleep and sleep habits. Qian said this is the first study to his knowledge to use a nationally representative population to look at how several sleep behaviors, and not just sleep duration, might influence life expectancy.

About two-thirds of study participants self-reported as being White, 14.5% Hispanic, 12.6% Black and 5.5% Asian. Because researchers were able to link participants to the National Death Index records (through December 31, 2019), they could examine the association between individual and combined sleep factors and all-cause and cause-specific mortality. Participants were followed for a median of 4.3 years during which time 8,681 individuals died. Of these deaths, 2,610 deaths (30%) were from cardiovascular disease, 2,052 (24%) were from cancer and 4,019 (46%) were due to other causes.

Researchers assessed ?ve different factors of quality sleep using a low-risk sleep score they created based on answers collected as part of the survey. Factors included: 1) ideal sleep duration of seven to eight hours a night; 2) difficulty falling asleep no more than two times a week; 3) trouble staying asleep no more than two times a week; 4) not using any sleep medication; and 5) feeling well rested after waking up at least five days a week. Each factor was assigned zero or one point for each, for a maximum of five points, which indicated the highest quality sleep.

“If people have all these ideal sleep behaviors, they are more likely to live longer,” Qian said. “So, if we can improve sleep overall, and identifying sleep disorders is especially important, we may be able to prevent some of this premature mortality.”

For the analysis, researchers controlled for other factors that may have heightened the risk of dying, including lower socioeconomic status, smoking and alcohol consumption and other medical conditions. Compared to individuals who had zero to one favorable sleep factors, those who had all five were 30% less likely to die for any reason, 21% less likely to die from cardiovascular disease, 19% less likely to die from cancer, and 40% less likely to die of causes other than heart disease or cancer. Qian said these other deaths are likely due to accidents, infections or neurodegenerative diseases, such as dementia and Parkinson’s disease, but more research is needed.

Among men and women who reported having all five quality sleep measures (a score of five), life expectancy was 4.7 years greater for men and 2.4 years greater for women compared with those who had none or only one of the five favorable elements of low-risk sleep. More research is needed to determine why men with all five low-risk sleep factors had double the increase in life expectancy compared with women who had the same quality sleep.

“Even from a young age, if people can develop these good sleep habits of getting enough sleep, making sure they are sleeping without too many distractions and have good sleep hygiene overall, it can greatly benefit their overall long-term health,” Qian said, adding that for the present analysis they estimated gains in life expectancy starting at age 30, but the model can be used to predict gains at older ages too. “It’s important for younger people to understand that a lot of health behaviors are cumulative over time. Just like we like to say, ‘it’s never too late to exercise or stop smoking,’ it’s also never too early. And we should be talking about and assessing sleep more often.”

These sleep habits can be easily asked about during clinical encounters, and the researchers hope patients and clinicians will start talking about sleep as part of their overall health assessment and disease management planning.  

One limitation of the study is that sleep habits were self-reported and not objectively measured or verified. In addition, no information was available about the types of sleep aid or medicine used or how often or long participants used them. Future research is needed to understand how these gains in life expectancy might continue as people age, as well as further explore the sex differences that were observed.

Previous studies have shown that getting too little or too much sleep can negatively affect the heart. It’s also been widely reported that sleep apnea, a sleep disorder that causes someone to pause or stop breathing while asleep, can lead to a number of heart conditions, including high blood pressure, atrial fibrillation and heart attacks.

Qian will present the study, “Low-risk Sleep Patterns, Mortality, and Life Expectancy at Age 30 Years: A Prospective Study of 172,321 U.S. Adults,” on Monday, March 6, at 12:45 p.m. CT / 18:45 UTC in Prevention and Health Promotion Moderated Poster Theater 10, Hall F.

ACC.23/WCC will take place March 4-6, 2023, in New Orleans, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC23/#WCCardio for the latest news from the meeting.

The American College of Cardiology (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of JACC Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at ACC.org,

###

Media Contacts