Shirley Ryan AbilityLab receives $8.7 Million NIH grant for first-of-its-kind bionic arm osseointegration study

Study has potential to restore sensation for those with upper-limb amputations

Grant and Award Announcement

SHIRLEY RYAN ABILITYLAB

Today, an estimated 41,000 people in the United States live with the loss of an upper limb, including hundreds of service men and women. Although significant progress has been made in the durability, control and function of upper-limb prosthetic devices, they lack complete integration into the body and, importantly, do not enable their users to feel.

Now, with the award of an $8.7 million grant from the National Institutes of Health (NIH), Shirley Ryan AbilityLab — the top-ranked physical medicine and rehabilitation hospital — and its research partners have an opportunity to significantly advance the field of bionics by applying osseointegration in a novel manner.

Osseointegration is a technique whereby a metal implant is surgically attached to a person’s residual bone. The implant then becomes an integrated extension of the body — providing a direct attachment between the bionic and residual limb. Then, a special system called e-OPRA (Enhanced Osseoanchored Prostheses for the Rehabilitation of Amputees) uses electrodes implanted into muscle to provide robust sensory feedback through peripheral nerve stimulation, restoring the feeling of touch.

The study is the first to combine osseointegration, targeted muscle reinnervation (TMR) and pattern-recognition control using implanted electromyographic (EMG) sensors. (TMR is a revolutionary surgical technique — that was developed by collaborators at Northwestern Medicine and Shirley Ryan AbilityLab — to allow those with amputations control of bionic prostheses.) It also is the first in-home trial of the e-OPRA system in people with upper-limb amputations who have had TMR surgery and use a Coapt Gen2 pattern recognition–controlled myoelectric prosthesis.  

“With this combination of novel and advanced technologies, the device should feel much more like a person’s actual limb,” said Levi Hargrove, the study’s lead researcher and director of the Regenstein Foundation Center for Bionic Medicine at Shirley Ryan AbilityLab. “This study builds on many years of our
leadership in bionic medicine, and marks a significant step forward in making this intuitive technology broadly available for the first time.”

As part of the study, Shirley Ryan Ability is partnering with Integrum, a Swedish company that invented the osseointegration technique, and Northwestern Medicine, which will implant the device and perform TMR surgery on eight research subjects. Researchers at UChicagoMedicine and Bionics Institute in Australia also will support the study.

Following the surgeries, the research team will lead two clinical trials to evaluate the comfort and function with implanted electrodes through e-OPRA — compared to and combined with the state-of-the-art clinical solution using Coapt’s Gen2 pattern recognition system — and to evaluate the effects of providing sensory feedback.

“Engineers, material scientists, neurophysiologists and surgeons have never before come together on this scale to apply osseointegration in this manner,” said Rickard Branemark, CEO and founder of Integrum AB. “We are very excited to collaborate on this important work.”

The five-year grant is being funded through the NIH’s UG3 and UH3 mechanisms, which specifically are targeted to translating groundbreaking neural technologies for patients.

The award comes on the heels of another, recently funded $1.5 million U.S. Department of Defense grant for Shirley Ryan AbilityLab and its research collaborators to evaluate functional mobility, neural control and user satisfaction as they relate to osseointegration in bionic legs.

About Shirley Ryan AbilityLab

Shirley Ryan AbilityLab, formerly the Rehabilitation Institute of Chicago (RIC), is the global leader in physical medicine and rehabilitation for adults and children with the most severe, complex conditions — from traumatic brain and spinal cord injury to stroke, amputation and cancer-related impairment. The organization expands and accelerates leadership in the field that began at RIC in 1953. The quality of its care has led to the designation of “No. 1 Rehabilitation Hospital in America” by U.S. News & World Report every year since 1991. Upon opening in March 2017, the $550 million, 1.2-million-square-foot Shirley Ryan AbilityLab became the first-ever “translational” research hospital in which clinicians, scientists, innovators and technologists work together in the same space, surrounding patients, discovering new approaches and applying (or “translating”) research real time. This unique model enables patients to have 24/7 access to the brightest minds, the latest research and the best opportunity for recovery. Shirley Ryan AbilityLab is a 501 (c)(3) nonprofit organization. For more information, go to www.sralab.org. 

 

About Integrum

Integrum AB is a publicly traded company (INTEG B: Nasdaq First North Growth Market) based outside of Gothenburg, Sweden, with a U.S. subsidiary in San Francisco, CA. Since 1990, osseointegration, the science behind the OPRA™ Implant System, has been helping individuals with amputations enjoy a dramatically improved quality of life. Thorough surgical experience gained over more than three decades, from more than 500 surgeries, in 14 countries, has led to the development of Integrum’s system for bone-anchored prostheses — a vastly superior alternative to the traditionally used socket prosthesis. For more information, please visit www.integrum.se.

 

Ground-breaking findings bring hope for faster and better recovery after stroke

Peer-Reviewed Publication

UNIVERSITY OF GOTHENBURG

 

IMAGE: REHABILITATION AFTER STROKE. view more 

CREDIT: PHOTO: UNIVERSITY OF GOTHENBURG

An effective treatment for most stroke victims — even those who, today, are unable to gain access to care within the first few hours. This is the goal of an experimental method that has been tested with great success in an international study headed by the University of Gothenburg.

The work now published in the Journal of Clinical Investigation is a multicenter study in which researchers at the Universities of Gothenburg and Cologne implemented parallel testing of an experimental stroke treatment on mice. The study was conducted in collaboration with researchers at the Czech Academy of Sciences.

By giving mice a molecule, the complement peptide C3a, in nasal drops, the scientists saw them recover motor function faster and better after stroke compared with mice that had received nasal drops with placebo. These results confirm and extend a previous study at the University of Gothenburg and the current study design further strengthens their credibility.

“We see the same positive effects in experiments done in Sweden and in Germany, which makes the results much more robust,” says Marcela Pekna, Professor of Neuroimmunology at Sahlgrenska Academy, University of Gothenburg, who led the study.

No racing against time

One crucial point is that the treatment was not initiated until seven days after the stroke. In a conceivable future, most stroke patients could thus be included — even those who do not reach hospital in time or who, for other reasons, are not helped by clot-dissolving drugs (thrombolysis) or mechanical clot removal (thrombectomy).

“With this method, there’s no need to race against the clock. If the treatment is used in clinical practice, all stroke patients could receive it, even those who arrive at the hospital too late for thrombolysis or thrombectomy. Those who have remaining disability after the clot is removed could improve with this treatment too,” Pekna says.

The study demonstrates not only very distinct positive effects, but also identifies the underlying cellular and molecular processes in the brain. Magnetic resonance imaging (MRI) showed that the treatment with C3a peptide increased the formation of new connections among nerve cells in the mouse brains.

Mechanisms clarified

Milos Pekny, Professor at the Department of Clinical Neuroscience at Sahlgrenska Academy, University of Gothenburg, participated in the study.

“Our results show,” he says, “that the C3a peptide affects the function of astrocytes — that is, cells that control many of the nerve cells' functions in both the healthy and the diseased brain — and which signals astrocytes send to nerve cells.”

Despite advances in emergency care, the most common form of stroke, ischemic stroke, is still a major cause of long-term disability, including impaired speech and mobility. The researchers emphasize that stroke treatment is not solely a matter of prompt interventions in the first hours after symptom onset.

“There is great potential for substantial improvement even at a later stage. Since the molecule was administered in nasal drops, the treatment could be given at home by relatives or the patients themselves,” Pekny says.

Timing is also of importance when it comes to the C3a peptide treatment. If the molecule is given too soon, it might increase the amount of inflammatory cells in the brain. The study also shows that the positive outcomes in experimental animals persist long after the treatment is discontinued.

“The good effect remains,” Pekna says, “and that is important. It means that this is real. And we know more about how the C3a peptide works. Our ambition is to develop the method to make it usable in clinical practice, but to get there, and especially to be able to carry out the necessary clinical trials, we need to team up with a partner in the pharmaceutical industry,” she concludes.

Astrocytes are cells that control many of the nerve cells' functions in both the healthy and the diseased brain.

CREDIT

Photo: University of Gothenburg.

JOURNAL

Journal of Clinical Investigation

DOI

10.1172/JCI162253 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity

Sleep apnoea link to cognitive decline raises need for targeted treatment options

Peer-Reviewed Publication

FLINDERS UNIVERSITY

 

IMAGE: ASSOCIATE PROFESSOR ANDREW VAKULIN IS SEARCHING FOR SOLUTIONS TO SLEEP DISORDERS WITH THE FLINDERS HEALTH AND MEDICAL RESEARCH INSTITUTE SLEEP HEALTH GROUP. view more 

CREDIT: THE HOSPITAL RESEARCH FOUNDATION

Flinders University experts are working on better solutions for sleep apnoea to ward off a range of health risks, including cognitive decline.

Improved solutions for obstructive sleep apnoea (OSA), insomnia and other sleep disorders are being developed by the Flinders Sleep Health experts to reduce the associated negative health effects such as cardiovascular harm, diabetes, anxiety and depression and even long-term cognitive decline.

Heightened risk of cognitive function decline from undiagnosed OSA – particularly in middle-aged men living in the community – is the focus of one of the latest studies published in Sleep Health.

The study recorded the sleep patterns of more than 470 men aged from 41-87 years along side their daytime cognitive function for processing speed, visual attention, episodic memory recollection and other markers.

Measuring distinct features of brain electrical activity during non-REM sleep, called ‘sleep spindles’, the study aimed to explore if these features can serve as markers of cognitive function.

“Non-REM sleep includes light stage 1 and 2 sleep, as well as deeper stage 3 sleep which is thought to play an important role in learning and memory,” says Flinders University sleep researcher Dr Jesse Parker.

“Our study found cross-sectional associations between various domains of next-day cognitive function and several sleep spindle metrics during stage 2 and stage 3 of their sleep cycle.

“The presence and severity of OSA was an important factor in this relationship.”

While standard clinical tests for OSA may detect and help to improve this common sleep-related breathing disorder with interventions such as continuous positive airway pressure (CPAP) or specific dental devices, the condition does vary between people depending on gender, age and other factors.

Based on this latest Florey Adelaide Male Ageing Study results, the Flinders Health and Medical Research Institute Sleep Health researchers recommend long-term investigations into sleep spindle phases and OSA to improve future treatments – and to determine whether OSA interventions such as CPAP do improve sleep quality and cognitive function.

Sleep apnoea affects more than 1 billion people globally and if untreated or severe may increase the risk of dementia and Parkinson’s disease, hypertension, cardiovascular disease, anxiety and depression, reduced quality of life, traffic accidents and all-cause mortality, previous research has found. In Australia alone, the economic cost associated with poor sleep including sleep disorders has been estimated at $66 billion a year.

“Poor sleep as a result of OSA, as well as delayed sleep and body clock disruption, may lead to chronic health conditions, including cognitive impairment, poor mental health and cardiovascular disease,” says Associate Professor Andrew Vakulin, senior author on the publication and Flinders Health and Medical Research Institute (FHMRI) Sleep Health researcher.

“Highlighting the need for better treatments, our latest studies not only make more links between sleep disorders and poor health outcomes but also the need for tailored specific treatments for individual cases, including co-occurring conditions such as insomnia and sleep apnoea.

"Along with uncontrolled hypertension, this latest study also clearly links cognitive function to sleep in adult males, possibly made worse by undiagnosed moderate to severe OSA,” says Associate Professor Vakulin

The article, The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study (2023) by Jesse Parker, Sarah L Appleton, Robert J Adams, Yohannes Adama Melaku, Angela d’Rozario, Gary A Wittert, Sean Martin, Peter G Catcheside, Bastien Lechat, Alison Jane Teare, Barbara Toson and Andrew Vakulin has been published in Sleep Health. DOI:  10.1016/j.sleh.2023.03.007

Also, Associations of Baseline Sleep Microarchitecture with Cognitive Function After 8 Years in Middle-Aged and Older Men from a Community-Based Cohort Study (2023) published in Nature and Science of Sleep DOI: 10.2147/NSS.S401655

Acknowledgements: The work was supported by the Australian NHMRC and Hospital Research Foundation grants, as well as the ResMed Foundation, USA for the EEG analysis.

The Flinders Health and Medical Research Institute Sleep Health group is also investigating other interventions to tackle sleep apnea including a range of clinical trials of alternative drug therapies – including the publications at the links below:

From novel devices and cognitive behavioural therapy to complementary muscle, sedative and other drug treatments, the latest round of studies from Flinders Sleep Health group are exploring more targeted treatments.

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JOURNAL

Sleep Health

DOI

10.1016/j.sleh.2023.03.007 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The association between sleep spindles and cognitive function in middle-aged and older men from a community-based cohort study

 

Colorful foods improve athletes’ vision

Visual range is a critical asset for top athletes in almost any sport

Peer-Reviewed Publication

UNIVERSITY OF GEORGIA

Nutrition is an important part of any top athlete’s training program. And now, a new study by researchers from the University of Georgia proposes that supplementing the diet of athletes with colorful fruits and vegetables could improve their visual range.

The paper, which was published in Exercise and Sport Sciences Reviews, examines how a group of plant compounds that build up in the retina, known as macular pigments, work to improve eye health and functional vision.

Previous studies done by UGA researchers Billy R. Hammond and Lisa Renzi-Hammond have shown that eating foods like dark leafy greens or yellow and orange vegetables, which contain high levels of the plant compounds lutein and zeaxanthin, improves eye and brain health.

“A lot of the research into macular lutein and zeaxanthin has focused on health benefits, but from a functional perspective, higher concentrations of these plant pigments improve many aspects of visual and cognitive ability. In this paper, we discuss their ability to improve vision in the far distance or visual range,” said lead author Jack Harth, a doctoral candidate in UGA’s College of Public Health.

Visual range, or how well a person can see a target clearly over distance, is a critical asset for top athletes in almost any sport.

The reason why objects get harder to see and appear fuzzier the farther they are from our eyes is thanks in part to the effects of blue light.

“From a center fielder's perspective, if that ball's coming up in the air, it will be seen against a background of bright blue sky, or against a gray background if it's a cloudy day. Either way, the target is obscured by atmospheric interference coming into that path of the light,” said Harth.

Many athletes already take measures to reduce the impact of blue light through eye black or blue blocker sunglasses, but eating more foods rich in lutein and zeaxanthin can improve the eye’s natural ability to handle blue light exposure, said Harth.

When a person absorbs lutein and zeaxanthin, the compounds collect as yellow pigments in the retina and act as a filter to prevent blue light from entering the eye.

Previous work had been done testing the visual range ability of pilots in the 1980s, and Hammond and Renzi-Hammond have done more recent studies on how macular pigment density, or how much yellow pigment is built up in the retina, is linked to a number of measures of eye health and functional vision tests.

“In a long series of studies, we have shown that increasing amounts of lutein and zeaxanthin in the retina and brain decrease glare disability and discomfort and improve chromatic contrast and visual-motor reaction time, and supplementing these compounds facilitates executive functions like problem-solving and memory. All of these tasks are particularly important for athletes,” said corresponding author Billy R. Hammond, a professor of psychology in the Behavior and Brain Sciences Program at UGA’s Franklin College of Arts and Sciences.

This paper, Harth said, brings the research on these links between macular pigment and functional vision up to date and asks what the evidence suggests about optimizing athletic performance.

“We're at a point where we can say we've seen visual range differences in pilots that match the differences found in modeling, and now, we've also seen it in laboratory tests, and a future goal would be to actually bring people outside and to measure their ability to see contrast over distance through real blue haze and in outdoor environments,” said Harth.

But before you start chowing down on kale in the hopes of improving your game, he cautions that everybody is different. That could mean the way our bodies absorb and use lutein and zeaxanthin varies, and it could take a while before you notice any improvements, if at all.

Still, the evidence of the overall health benefits of consuming more lutein and zeaxanthin are reason enough to add more color to your diet, say the authors.

“We have data from modeling and empirical studies showing that higher macular pigment in your retina will improve your ability to see over distance. The application for athletes is clear,” said Harth.

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JOURNAL

Exercise and Sport Sciences Reviews

DOI

10.1249/JES.0000000000000318 

ARTICLE TITLE

A Dietary Strategy for Optimizing the Visual Range of Athletes

Diet tracking: How much is enough to lose weight?

'You don't need to have perfect tracking every day to lose a clinically significant amount of weight'

Peer-Reviewed Publication

UNIVERSITY OF CONNECTICUT

Keeping track of everything you eat and drink in a day is a tedious task that is tough to keep up with over time. Unfortunately, dutiful tracking is a vital component for successful weight loss, however, a new study in Obesity finds that perfect tracking is not needed to achieve significant weight loss.

Researchers from UConn, the University of Florida, and the University of Pennsylvania tracked 153 weight loss program participants for six months where users self-reported their food intake using a commercial digital weight loss program. The researchers wanted to see what the optimal thresholds were for diet tracking to predict 3%, 5%, and 10% weight loss after six months.

“We partnered with WeightWatchers, who was planning on releasing a new Personal Points program, and they wanted to get empirical data via our clinical trial,” says co-author and Department of Allied Health Sciences Professor Sherry Pagoto.

Pagoto explains that the new program takes a personalized approach to assigning points including a list of zero-point foods to eliminate the need for calculating calories for everything,

“Dietary tracking is a cornerstone of all weight loss interventions, and it tends to be the biggest predictor of outcomes. This program lowers the burden of that task by allowing zero-point foods, which do not need to be tracked.”

Researchers and developers are seeking ways to make the tracking process less burdensome, because as Pagoto says, for a lot of programs, users may feel like they need to count calories for the rest of their lives: “That’s just not sustainable. Do users need to track everything every single day or not necessarily?”

With six months of data, Assistant Professor in the Department of Allied Health Sciences Ran Xu was interested to see if there was a way to predict outcomes based on how much diet tracking participants did. Ran Xu and Allied Health Sciences Ph.D. student Richard Bannor analyzed the data to see if there were patterns associated with weight loss success from a data science perspective. Using a method called receiver operating characteristics (ROC) curve analysis they found how many days people need to track their food to reach clinically significant weight loss.

“It turns out, you don’t need to track 100% each day to be successful,” says Xu. “Specifically in this trial, we find that people only need to track around 30% of the days to lose more than 3% weight and 40% of the days to lose more than 5% weight, or almost 70% of days to lose more than 10% weight. The key point here is that you don’t need to track every day to lose a clinically significant amount of weight.”

This is promising since Pagoto points out that the goal for a six-month weight loss program is typically 5% to 10%, a range where health benefits have been seen in clinical trials.

“A lot of times people feel like they need to lose 50 pounds to get healthier, but actually we start to see changes in things like blood pressure, lipids, cardiovascular disease risk, and diabetes risk when people lose about 5-to-10% of their weight,” says Pagoto. “That can be accomplished if participants lose about one to two pounds a week, which is considered a healthy pace of weight loss.”

Xu then looked at trajectories of diet tracking over the six months of the program.

The researchers found three distinct trajectories. One they call high trackers, or super users, who tracked food on most days of the week throughout six months, and on average lost around 10% of their weight.

However, many participants belonged to a second group that started tracking regularly, before their tracking gradually declined over time to, by the four-month mark, only about one day per week. They still lost about 5% of their weight.

A third group, called the low trackers, started tracking only three days a week, and dropped to zero by three months, where they stayed for the rest of the intervention. On average this group lost only 2% of their weight.

“One thing that is interesting about this data is, oftentimes in the literature, researchers just look at whether there is a correlation between tracking and overall weight loss outcomes. Ran took a data science approach to the data and found there is more to the story,” Pagoto says. “Now we’re seeing different patterns of tracking. This will help us identify when to provide extra assistance and who will need it the most.”

The patterns could help inform future programs which could be tailored to help improve user tracking based on which group they fall into. Future studies will dig deeper into these patterns to understand why they arise and hopefully develop interventions to improve outcomes.

“For me, what’s exciting about these digital programs is that we have a digital footprint of participant behavior,” says Xu. “We can drill down to the nitty-gritty of what people do during these programs. The data can inform precision medicine approaches, where we can take this data science perspective, identify patterns of behavior, and design a targeted approach.”

Digitally delivered health programs give researchers multitudes of data they never had before which can yield new insights, but this science requires a multidisciplinary approach.

“Before, it felt like we were flying in the dark or just going by anecdotes or self-reported measures, but it’s different now that we have so much user data. We need data science to make sense of all these data. This is where team science is so important because clinical and data scientists think about the problem from very different perspectives, but together, we can produce insights that neither of us could do on our own. This must be the future of this work,” says Pagoto.

Xu agrees: “From a data science perspective, machine learning is exciting but if we just have machine learning, we only know what people do, but we don’t know why or what to do with this information. That’s where we need clinical scientists like Sherry to make sense of these results. That’s why team science is so important.”

No longer flying in the dark, these multi-disciplinary teams of researchers now have the tools needed to start tailoring programs even further to help people achieve their desired outcomes. For now, users of these apps can be assured that they can still get significant results, even if they miss some entries.

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JOURNAL

Obesity

DOI

10.1002/oby.23795 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

How much food tracking during a digital weight-management program is enough to produce clinically significant weight loss?

 

Single-cell atlas of the whole human lung

First integrated Human Lung Cell Atlas provides insights into lung diseases

Peer-Reviewed Publication

WELLCOME TRUST SANGER INSTITUTE

The largest and most comprehensive cell map of the human lung is announced in Nature Medicine today (8 June).  Revealing the great diversity of cell types in the lung and key differences between health and disease, the Human Lung Cell Atlas will be a valuable resource for lung researchers.

By combining data from nearly 40 studies, researchers created the first integrated single-cell atlas of the lung, revealing rare cell types and highlighting cellular differences between healthy people. In addition, the study found common cell states between lung fibrosis, cancer and COVID-19, offering new ways of understanding lung disease, which could help identify new therapeutic targets.

The study is part of the global Human Cell Atlas* (HCA) initiative to map every cell type in the human body, to transform our understanding of health, infection and disease.

Lung research has benefited greatly from recent single-cell studies that show which genes are active in each cell. Despite this, the research has been limited so far by the number of samples and individuals included per study. To better understand healthy lungs and determine what goes wrong in disease, a comprehensive atlas has been needed, however this has been difficult to achieve.

Now, a large team of researchers has successfully combined 49 lung datasets, from nearly 40 separate studies, into a single integrated Atlas, using advanced machine learning.  By pooling and integrating datasets from every major single-cell RNA-sequencing lung study published to date, the team created the first integrated Human Lung Cell Atlas. This Atlas spans over 2.4 million cells from 486 individuals and gives new insights into lung biology that were not possible before.

Dr Malte Luecken, a senior author on the paper and Group leader at the Institute of Computational Biology and the Institute of Lung Health and Immunity at Helmholtz Munich, Germany, said: “A comprehensive organ atlas requires many datasets to capture the diversity between both cells and individuals, but combining different datasets is a huge challenge. We developed a benchmarking pipeline to find the optimal method to integrate all datasets into the Atlas, using artificial intelligence, and successfully combined knowledge and data from almost 40 previous lung studies.”

Professor Fabian Theis, a senior author on the paper and Director of the Institute of Computational Biology at Helmholtz Munich, said: “We have created a first reference atlas of the human lung, which includes data from more than a hundred healthy people and reveals how the cells from individuals vary with age, sex, and smoking history. The sheer numbers of cells and individuals involved now gives the power to see rare cell types and identify new cell states that have not previously been described.”

While the core of the Human Lung Cell Atlas is data from healthy lungs, the team also took datasets from more than 10 different lung diseases and projected these onto the healthy data, to understand disease states.

The team discovered that different lung diseases shared common immune cell states, including the finding that a subset of macrophages (a type of immune cell) shared similar gene activity in lung fibrosis, cancer and COVID-19. The shared states indicate that these cells could play a similar role in scar formation in the lung in all three diseases, and provide pointers for potential therapeutic targets. 

Professor Martijn Nawijn, a senior author on the paper and Professor at the University Medical Center Groningen, the Netherlands, said: “This is the first effort to compare healthy and diseased lungs in one study in an integrated way.  Our study not only supports the presence of lung fibrosis in COVID-19, it allows us to identify and define a shared cell state between lung fibrosis, COVID-19 and lung cancer patients.  Finding these shared disease-associated cells is really exciting, and reveals a totally different way of looking at lung diseases, opening possibilities for novel treatment targets and developing treatment response biomarkers. Our findings also suggest that therapies working for one disease may help alleviate others.”

The Lung Atlas Integration project was an international collaborative effort with nearly 100 partners from more than 60 departments, including key researchers from Helmholtz Munich, University Medical Center Groningen and Northwestern University. The team are part of the Human Cell Atlas Lung Biological Network**, which has its roots in the Chan Zuckerberg Initiative Seed Networks for the Human Cell Atlas, and the European Union funded lung network DiscovAIR. At the start of the COVID-19 pandemic in 2020, the single-cell lung communities came together rapidly, forming the HCA Lung Biological Network to help understand COVID-19, which then led to the global effort to integrate all the data.

Lisa Sikkema, the first author on the paper and PhD student at the Institute of Computational Biology at Helmholtz Munich, said: “One of the big problems in creating the integrated lung cell atlas was with cell type annotation. Different research groups used different names for the same cell type, or the same name for different cells, so as a team we worked to standardise them using the data in the atlas. The atlas is a first step towards a consensus annotation of the human lung, which will help bring together the field of lung research.”

The first integrated major organ within the Human Cell Atlas initiative, the Human Lung Cell Atlas is publically available for researchers globally, as a central resource to study the lung in health and disease.

Dr Alexander Misharin, a senior author on the paper and Associate Professor at Northwestern University Feinberg School of Medicine, USA, said: “The Human Lung Cell Atlas is a huge resource for the scientific and medical community. Openly available to researchers, new disease data can be mapped onto the HLCA, transforming research into lung biology and disease. As the first whole reference atlas of a major organ, the HLCA also represents a milestone towards achieving a full Human Cell Atlas which will transform our understanding of biology and disease and lay the foundation for a new era of healthcare”.

ENDS

Contact Details:
Dr Samantha Wynne,
Human Cell Atlas Scientific Communications Manager,
HCA UK Office, Wellcome Sanger Institute,
Cambridge, CB10 1SA, UK
Email: press@humancellatlas.org
 

Notes to Editors:

*The Human Cell Atlas (HCA)
The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.

The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 2,900 HCA members, from 94 countries around the world. https://www.humancellatlas.org

**The Human Cell Atlas Lung Biological Network is a group of scientists who collaborate to map the cell types and states present in human airways. This group is coordinated by Pascal Barbry, Alexander Misharin, Martijn Nawijn and Jay Rajagopal.

Publication:
An integrated cell atlas of the lung in health and disease. Lisa Sikkema et al. (2023). Nature Medicine. DOI :10.1038/s41591-023-02327-2

Funding:
This work was supported by many funders including: The Chan Zuckerberg Initiative, European Union H2020 (Discovair), Fondation pour la Recherche Médicale, National Infrastructure France Génomique, Wellcome, The Netherlands Lung Foundation, The German Center for Lung Research, the Helmholtz Association and the European Respiratory Society. Please see the paper for full list of funders.

Selected Websites:

Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en [helmholtz-munich.de] 

University Medical Center Groningen
The University Medical Center Groningen (UMCG) is one of the largest hospitals in the Netherlands and is the largest employer in the Northern Netherlands. More
characterized by a combination of fundamental and patient oriented clinical research. The interaction between these two stimulates the development of new clinical and research opportunities. Problems that occur in the clinical practice act as a catalyst which sets new fundamental research in motion, whereas fundamental research can come up with new clinical possibilities. The UMCG focuses on healthy ageing in all priority areas: research, clinical care and education. Together we push boundaries for a sustainable future of health. https://umcgresearch.org/

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JOURNAL

Nature Medicine

DOI

10.1038/s41591-023-02327-2 

METHOD OF RESEARCH

Meta-analysis

SUBJECT OF RESEARCH

Human tissue samples

ARTICLE TITLE

An integrated cell atlas of the lung in health and disease

ARTICLE PUBLICATION DATE

8-Jun-2023

Mouse models of adolescent binge drinking reveal key long-lasting brain changes

Peer-Reviewed Publication

PENN STATE

 

IMAGE: PENN STATE NEUROSCIENCE DOCTORAL STUDENT AVERY SICHER WORKS IN THE LAB, DOING PATCH-CLAMP ELECTROPHYSIOLOGY. view more 

CREDIT: DAN LESHER / PENN STATE

UNIVERSITY PARK, Pa — Heavy alcohol consumption may cause permanent dysregulation of neurons, or brain cells, in adolescents, according to a new study in mice. The findings suggest that exposure to binge-levels of alcohol during adolescence, when the brain is still developing, lead to long-lasting changes in the brain’s ability to signal and communicate — potentially setting the stage for long-term behavioral changes and hinting towards the mechanisms of alcohol-induced cognitive changes in humans.

“What we’re seeing here,” said Nikki Crowley, assistant professor in biology and biomedical engineering and Huck Early Chair in Neurobiology and Neural Engineering, “is that if adolescent binge drinking knocks neurons off this trajectory, they might not be able to get back, even if the alcohol consumption stops.”

The prefrontal cortex is a key brain region for executive functioning, risk assessment and decision-making. According to Crowley, it’s not fully formed in adolescents and is still maturing in humans until around age 25. Disruptions to its development in young people may have serious and long-lasting consequences, added Crowley.

“Heavy binge drinking is problematic for everyone, and should be avoided, but adolescent brains appear to be particularly vulnerable to the consequences, which in humans, will follow them for decades,” Crowley said.

The team, led by Avery Sicher, a doctoral student in Penn State’s neuroscience program, used a model of adolescent ethanol exposure in mice to understand how different populations of neurons in the cortex, the outermost layer of the brain, are changed by voluntary binge alcohol consumption. In this model, mice are known to consume alcohol in patterns that approximate human binge drinking — defined by the National Institute on Alcohol Abuse and Alcoholism as a pattern of alcohol consumption that leads to a blood alcohol concentration of 0.08% or higher, usually in about two hours. Binge drinking is considered to be one of the most dangerous patterns of alcohol misuse, and understanding its impact on the developing brain can help inform treatment.

Sicher and her colleagues gave mice access to alcohol during a 30-day period. Due to their faster development and shorter lifespan, this corresponded to roughly ages 11-18 in human years. They then looked at the electrophysiological properties of different neurons throughout the prefrontal cortex to understand how adolescent binge drinking influenced the wiring and firing of these circuits. Sicher et al. used whole-cell patch clamp electrophysiology, combined with techniques such as optogenetics, which allowed the team to isolate individual neurons and record measurements related to intrinsic excitability, such as the resting membrane potential and the ability for each neuron to fire action potentials. This allowed them to understand how these neurons had changed their ability to signal with other neurons.

They found that somatostatin neurons, a key population of cells that provides inhibition of neurotransmitter release from other cell types throughout the brain and helps to “dampen the noise,” appeared to be permanently dysregulated in the mice that binge drank as compared to mice that were only provided water throughout development. Somatostatin neurons release both inhibitory neurotransmitters, like GABA, as well as inhibitory peptides like somatostatin, and proper functioning of these neurons is necessary for a healthy brain. The neurons were more excitable — meaning they were signaling too much and dampening the activity of other key neurons — as far out as 30 days after the mice stopped drinking alcohol, when the mice have transitioned into adulthood.

“Neurons have a relatively fixed developmental trajectory — they need to get where they are going and sync up with the right partners during specific periods of development in order to function properly,” explained Crowley.

David Starnes, an undergraduate biology student in Schreyer’s Honor College, performed somatostatin cell counts to quantify cell density before and after ethanol consumption. He found that while the electrophysiology data suggested these neurons wire differently, the number of SST neurons does not appear to change as a result of binge drinking.

Other authors on the paper include Keith Griffith, a research technician in the lab and former undergraduate in Engineering Science and Mechanics, Grace Smith, a graduate student in Biomedical Engineering, Dakota Brockway, a graduate student in neuroscience, and Nigel Dao, a former research technician in the lab and current doctoral student at New York University. This research was supported by the National Institutes of Health and the Huck Institutes of the Life Sciences at Penn State.

To learn more about Sicher’s neuroscience research, watch this short video from the Huck Institutes’ Student Spotlight series. The paper is currently available in the online version of the journal Neuropharmacology and will be published in the Aug. 15 issue.

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DOI

10.1016/j.neuropharm.2023.109561