Publisher Health

Schwann cells are known to protect and repair nerve cells. Until now, however, it was not known that they themselves take over functions of certain immune cells during nerve healing. For example, they produce signaling molecules that can activate other immune cells. In particular, however, they are able to stop inflammatory reactions in order to prevent excessive tissue damage and allow the nerve to regenerate.
“This is essential, because inflammation releases free radicals against which nerve fibers cannot protect themselves. Therefore, the inflammation must be cleared quickly, which is precisely what Schwann cells do,” explains Dr. Sabine Taschner-Mandl, who designed the study and heads a research group at St. Anna CCRI. The new results, in which the Medical University of Vienna is also significantly involved, were published in the journal Glia.
Do Schwann cells protect against malignancy?
How are these results related to tumor growth? After nerve injury, Schwann cells adopt a “repair” mode that is also found in benign infantile nerve tumors. There, it causes the tumor cells to mature and thus reach a stage where they lose their aggressive properties and no longer divide unchecked (Weiss T., Taschner-Mandl S., et al., Nat Commun 2021).
“Based on the current results, we now suspect that the immune cell functions of Schwann cells also become effective in childhood nerve tumors. This is because in cancer, there is always a kind of inflammation bubbling away that never comes to a halt. In benign nerve tumors, ganglioneuromas, the accompanying chronic inflammation could be stopped by Schwann cells similar to nerve healing, because unlike malignancies, benign nerve tumors have many Schwann cells in their microenvironment. We also see that a lot of immune cells migrate into these tumors, for which the Schwann cells could also be responsible,” says Sabine Taschner-Mandl.
Healthy Inflammation: First Activate, Then Shut Down
In particular, the current study shows that Schwann cells can influence certain immune cells, so-called T cells, which play an important role in the defense against cancer. Schwann cells — both those in nerve regeneration and those in benign tumors — carry MHC-I and MHC-II molecules on their surface that are important for T-cell regulation. Via these molecules, Schwann cells present recognition features of material they have previously taken up from their environment.
We mimicked an inflammatory response in the laboratory and detected a whole range of additional stimulatory and inhibitory surface molecules that are also necessary for T cell activation,” explains Jakob Berner, MSc, co-first author of the study and interim PhD student in Kaan Boztug’s group at St. Anna CCRI. “Our experiments show that Schwann cells are able to take up large amounts of material via phagocytosis.”
As the first immune response to a nerve cut, Schwann cells secrete substances that attract T cells, macrophages and other immune cells. Now it turned out that not only a reaction between the classical immune cells takes place, but also between Schwann cells and T cells.
While Schwann cells initially fuel the inflammatory response by releasing interferon-gamma, they can later shut it down by up-regulating the T-cell inhibitory PD-L1 molecule.
“First activate, then shut down — that’s the normal process of an inflammatory response. If this were also the case in cancer, then it could curb cancer growth,” comments Sabine Taschner-Mandl. Whether and how these findings can be used for potential cancer therapies is now being researched.

The conventional wisdom is that medical and dental care are related, but less is known about how dental care relates to health outcomes after acute incidents like heart attacks.
To that end, University of Michigan researchers studied patients receiving periodontal care, dental cleanings or no dental care during 2016-2018 and who had acute myocardial infarction (heart attack) in 2017.
They found that patients who had heart attacks and received periodontal maintenance care had the shortest length of stay in the hospital, and more follow-up visits. The longest length of stay was experienced by the no-dental-care group.
“After controlling for several factors, the periodontal care group had higher odds of having post-hospital visits,” said study co-author Romesh Nalliah, associate dean for patient services at the U-M School of Dentistry.
There was no statistically significant difference between the other groups (active periodontal care and regular care) compared to the no-care group.
The study, published in the Journal of the American Dental Association, did not establish a causal relationship between periodontal disease and heart disease, but research like this adds weight to the understanding that there is an association between oral health and overall health, Nalliah said.
There are 800,000 myocardial infarctions in the United States annually, and those with periodontal disease are at increased risk for hospitalization after a heart attack, he said.
Nalliah and colleagues wanted to examine the association between periodontal care and heart attack hospitalization, and follow-up visits in the 30 days after acute care. Using the MarketScan database, they found 2,370 patients who fit the study criteria. Of those, 47% percent received regular or other oral health care, 7% received active periodontal care (root planing and periodontal scaling) and 10% received controlled periodontal care (maintenance). More than 36% did not have oral health care before they were hospitalized after a heart attack.
“Dentistry is often practiced in isolation from overall health care,” Nalliah said. “Our results add weight to the evidence that medical and dental health are closely interrelated. More and more studies like ours are showing that it is a mistake to practice medicine without the thoughtful consideration of the patient’s oral health.”
Nalliah said improved communication between medical and dental teams could help with early intervention to ensure stable periodontal health in patients who have risk factors for heart disease.
“It is important to include dental care in routine medical care and this means insurances must facilitate this connection rather than offer dental insurance as a separate add-on coverage,” he said.
Co-authors include Tanima Basu, senior statistician at the Michigan Hospital Medicine Safety Consortium, and Chiang-Hua Chang, research assistant professor at Michigan Medicine.
Story Source:
Materials provided by University of Michigan. Note: Content may be edited for style and length.

According to the National Birth Defects Prevention Network, one in every 8,000 to 10,000 births in the United States result in one of two congenital malformations of the ear: microtia (the child is born with only a cartilage stump for an ear) or anotia (the complete lack of an ear). Because there is no properly shaped ear canal or ear drum to capture and relay sound waves, a child with microtia or anotia usually has partial deafness as well.
Now, thanks to two novel tools developed by a Johns Hopkins Medicine resident and a former resident, the traditionally difficult surgery to create a replacement ear from a patient’s rib cartilage may soon be done faster, more simply and accurately, without wasting valuable tissue, and with the ability to “custom fit” the new organ for each patient.
“Although ear reconstruction surgery for repairing microtia and anotia in both pediatric and adult cases has been practiced for a number of years, it still is a demanding procedure for both the patient and the surgeon,” says Angelo Leto Barone, M.D., a former resident in plastic and reconstructive surgery at the Johns Hopkins University School of Medicine and now a craniofacial and pediatric plastic surgeon at Nemours Children’s Health in Orlando, Florida. “What makes it really difficult is that to construct a suitable ear requires a bit of artistic skill.”
To perform an ear reconstruction without needing such innate talent, Leto Barone and his colleague, Johns Hopkins interventional and diagnostic radiology surgery resident Anirudh Arun, M.D., invented two assistive devices using 3D manufacturing. The first is a simple to use carving tool that precisely slices rib cartilage removed from the patient to any desired thickness and minimizes tissue waste. The second is a “cookie-cutter-like” press using steel blades — shaped in patterns fashioned from a patient’s normal ear — to yield the pieces of cartilage that are brought together during surgery to form the new organ.
“The cartilage-slicing device basically doubles the amount of cartilage tissue available for surgery, meaning that less has to be harvested to safely produce the entire ear,” says Arun. “We only need two and a half ribs instead of the traditional four from prior techniques — less waste and less discomfort for the patient.”
Placed into the second cutter, the cartilage slices are precisely trimmed into the components of the new ear in minutes rather than the hours needed to do it manually with a scalpel.

A rare but potentially debilitating brain disorder finally has a definitive cause, thanks to research teams working on opposite sides of the globe.
A mutation in the gene that manages the transportation out of cells of zinc, an essential dietary micronutrient, is responsible for the disorder, called hypomyelinating leukodystrophy. The research, jointly led by Dr. Quasar Padiath at the University of Pittsburgh and Dr. Anju Shukla at the Kasturba Medical College in India, is reported in the journal Brain.
This is the first time that a mutation in a zinc transporter gene — in this case, TMEM163 — has been definitively linked to the development of any brain disorder, and it has the potential to provide insights into the role of zinc in normal brain development, injury and disease.
“Discovering a new gene responsible for causing a disease is always exciting; that feeling never gets old,” said Padiath, associate professor of human genetics and neurobiology at Pitt. “And finding out that a zinc transporter is really important for proper myelin development could have many clinical implications and offer new ways of treating other related neurological conditions.”
Hypomyelinating leukodystrophies are rare and often fatal neurological disorders caused by defects in genes involved in growth or maintenance of myelin, the fatty layer of insulation surrounding nerves that helps them transmit electrical impulses. As the myelin layer gradually gets thinner and is lost in these patients, nerve signals slow to a crawl, ushering in a slew of neurological problems, including impaired movement and balance control, muscle wasting, problems with vision, and hearing and memory loss.
While genes have been linked to leukodystrophies, the genetic underpinnings for the majority of cases are still unknown. To identify the root cause of a patient’s condition and recommend the most appropriate therapy, clinical neurologists often turn to researchers like Padiath.
By combing through patients’ genomes, Padiath looks for mutations and analyzes the effect of these mutations in cells and animal models, such as mice. Such an analysis is no small feat. To definitively link a new gene mutation to disease symptoms, multiple independent patient cases that share the same gene defect and clinical presentation have to be identified.
For rare diseases, such as hypomyelinating leukodystrophies, finding such cases is possible only by tapping a network of scientific and clinical collaborators from all over the world. In this study, the first patient sample came from Shukla, a professor of medical genetics at Manipal in southwest India. Inquiries to other groups in the U.S. and the Netherlands identified additional families who also carried mutations in the same gene.
A series of in-depth lab studies showed that the TMEM163 mutations impair the transporter’s ability to effectively shunt zinc from inside the cell, causing reduced production of proteins responsible for synthesis and maintenance of myelin and increasing cell death.
“Understanding how genes cause rare diseases is the first step in the process of finding treatments,” said Padiath. “It is important to remember that diseases that are rare in the global context are very important and real for patients and their families. Studying these diseases helps find cures and give hope to patients and valuable insights into therapeutic targets essential for normal cell functioning.”
Story Source:
Materials provided by University of Pittsburgh. Original written by Ana Gorelova. Note: Content may be edited for style and length.

Scientists have created a ‘digital mask’ that will allow facial images to be stored in medical records while preventing potentially sensitive personal biometric information from being extracted and shared.
In research published today in Nature Medicine, a team led by scientists from the University of Cambridge and Sun Yat-sen University in Guangzhou, China, used three-dimensional (3D) reconstruction and deep learning algorithms to erase identifiable features from facial images while retaining disease-relevant features needed for diagnosis.
Facial images can be useful for identifying signs of disease. For example, features such as deep forehead wrinkles and wrinkles around the eyes are significantly associated with coronary heart disease, while abnormal changes in eye movement can indicate poor visual function and visual cognitive developmental problems. However, facial images also inevitably record other biometric information about the patient, including their race, sex, age and mood.
With the increasing digitalisation of medical records comes the risk of data breaches. While most patient data can be anonymised, facial data is more difficult to anonymise while retaining essential information. Common methods, including blurring and cropping identifiable areas, may lose important disease-relevant information, yet even so cannot fully evade face recognition systems.
Due to privacy concerns, people often hesitate to share their medical data for public medical research or electronic health records, hindering the development of digital medical care.
Professor Haotian Lin from Sun Yat-sen University said: “During the COVID-19 pandemic, we had to turn to consultations over the phone or by video link rather than in person. Remote healthcare for eye diseases requires patients to share a large amount of digital facial information. Patients want to know that their potentially sensitive information is secure and that their privacy is protected.”
Professor Lin and colleagues developed a ‘digital mask’, which inputs an original video of a patient’s face and outputs a video based on the use of a deep learning algorithm and 3D reconstruction, while discarding as much of the patient’s personal biometric information as possible — and from which it was not possible to identify the individual.

Harvard Medical School scientists and colleagues at Stanford University have developed an artificial intelligence diagnostic tool that can detect diseases on chest X-rays directly from natural-language descriptions contained in accompanying clinical reports.
The step is deemed a major advance in clinical AI design because most current AI models require laborious human annotation of vast reams of data before the labeled data are fed into the model to train it.
A report on the work, published Sept. 15 in Nature Biomedical Engineering, shows that the model, called CheXzero, performed on par with human radiologists in its ability to detect pathologies on chest X-rays.
The team has made the code for the model publicly available for other researchers.
Most AI models require labeled datasets during their “training” so they can learn to correctly identify pathologies. This process is especially burdensome for medical image-interpretation tasks since it involves large-scale annotation by human clinicians, which is often expensive and time-consuming. For instance, to label a chest X-ray dataset, expert radiologists would have to look at hundreds of thousands of X-ray images one by one and explicitly annotate each one with the conditions detected. While more recent AI models have tried to address this labeling bottlenck by learning from unlabeled data in a “pre-training” stage, they eventually require fine-tuning on labeled data to achieve high performance.
By contrast, the new model is self-supervised, in the sense that it learns more independently, without the need for hand-labeled data before or after training. The model relies solely on chest X-rays and the English-language notes found in accompanying X-ray reports.

For the more than one million children attending New York City public schools, the likelihood of receiving COVID-19 vaccines depended on their race and ethnicity, and the borough in which they live.
In the first published analysis of school-level vaccination data, schools with majority Asian students had the highest vaccination rate for COVID-19 at 66.2 percent, followed by majority Hispanic schools at 53.5 percent, according to new research from NYU Grossman School of Medicine, Syracuse University, University of Delaware, and NYC’s Department of Health and Mental Hygiene. Lagging furthest behind in COVID vaccination rates were schools attended by majority White and Black students, at 44 percent, while schools in Staten Island had lower vaccination rates, on average, than in any other borough.
Reporting in the journal JAMA Network Open online September 15, after examining data from more than 1,500 NYC schools with an average of 980 students, the research team found that vaccination rates varied significantly by borough, ranging from the highest in Manhattan (59.7 percent) and lowest in Staten Island (38.6 percent). Additionally, the researchers found that middle-high schools were more highly vaccinated (64.9 percent) than elementary schools (38.8 percent).
When broken down further, the data showed that while majority Asian schools had the highest vaccination rates regardless of borough, majority White schools in Manhattan (61.9 percent) and Brooklyn (49.1 percent) were more highly vaccinated than majority White schools in the Bronx (34.1 percent), Queens (28.5 percent), or Staten Island (25.4 percent).
“While similar data have been examined for adults, we do not yet have a firm sense of how race and ethnicity influence vaccination for children,” says study lead investigator Brian D. Elbel, PhD, MPH, professor in the Departments of Population Health and Medicine at NYU Grossman School of Medicine. “Our new work finds that while some of the patterns seen in adults are present in children (high vaccination rates among Asian populations), there are large differences across various geographies of even a single city. Understanding these differences, including how policy and programmatic activities can address them, is important future work.”
According to the investigators, the study has a number of limitations. These include a school-level approach to collecting vaccine data, as well as the possibility that data on students receiving vaccinations outside of NYC may be missing.
Another limitation, acknowledged by Elbel, relates to the broad categorization of schools by majority race/ethnic groups. Further disaggregation by smaller ethnic subgroups was not possible given the analytic approach and data sources. For example, while Asians and Pacific Islanders make up 14 percent of NYC’s population, there is a high degree of heterogeneity across ethnic groups combined under the umbrella of Asian. This lack of data disaggregation for Asian or Hispanic ethnic subgroups may mask vaccination disparities within those communities.
According to the researchers, future analysis must examine the above trends using individual-level data that includes personal attitudes about vaccines, as well as the social, structural and political factors that influence vaccination rates among children to determine what policies or programs that can better address gaps in vaccine uptake.
Funding for the study was provided by the National Institutes of Nursing Research (NINR) of the National Institutes of Health grant U01 NR020443.
Besides Elbel, other NYU Langone researchers involved in this study are Eric Zhou, MA, and David Lee, MD, MS. Additional study co-investigators are Willy Chen, MA, at Syracuse University; Amy Ellen Schwartz, PhD, dean of the University of Delaware’s Joseph R. Biden Jr. School of Public Policy and Administration; and Sophia Day, MA, and Kevin Konty, PhD, at the New York City Department of Health and Mental Hygiene.

Fibrosis is a pathological proliferation of connective tissue that destroys the organ tissue. It is the ultimate consequence of almost every kind of chronic damage. Fibrosis can occur in almost every type of tissue in the body, although the liver, lungs, heart and kidneys are most often affected. Fibrosis is responsible for up to 45 percent of all mortality in industrialized countries. Inflammation or vascular disorders often cause chronic organ damage. They activate the fibroblasts, which then begin to proliferate uncontrollably and create deposits of fibrous tissue. This scars the organ tissue, destroying it little by little. The functioning of the affected organ worsens noticeably until it fails completely.
Eliminating activated fibroblasts while leaving resting cells undamaged
An international research team led by the University of Zurich (UZH) has now developed a new strategy to eliminate fibroblasts in a targeted manner. “In animals, we were able to trigger an immune response similar to that to a vaccination, in which the activated connective tissue cells were destroyed while the resting fibroblasts were left unharmed,” explains study leader Professor Christian Stockmann of the Institute of Anatomy at the University of Zurich. In this manner, researchers were able to reduce fibrosis in vital organs such as liver and lungs while at the same time leaving healthy tissue unharmed.
Difference in surface structures identified
This is where previous strategies for fibrosis treatment had previously failed, since they also damaged resting fibroblasts. Resting fibroblasts are important, however, for maintaining the structure and functioning of healthy tissue. Researchers therefore studied the differences between the surfaces of resting and of activated connective tissue cells. “Our computer-assisted analyses revealed that fragments of two surface proteins — Adam12 and Gli1 — which can be detected by the immune system, are present in large numbers on activated fibroblasts, while there are very few on the resting cells,” explains Stockmann. The activity of these two protein genes is stimulated by chronic tissue damage, which means the activated fibroblasts produce the said proteins in larger quantities.
Immunotherapy reduces lung and liver fibrosis in mice
The researchers then used these two surface structures as a vaccine in mice in order to trigger an immune response via cytotoxic T-cells. These immune cells normally eliminate virus-infected or cancerous cells. “With the newly developed immunotherapy, we were able to eliminate fibroblasts efficiently in mice, thus reducing fibrosis in the liver and the lungs, without affecting healthy organ tissue,” says Stockmann. If scientists manage to successfully trigger a comparable, targeted immune response in humans, then vaccine-based immunotherapy could be used in future for the treatment of patients with organ fibrosis.
Story Source:
Materials provided by University of Zurich. Note: Content may be edited for style and length.

Faecal microbiota transplantation (FMT) — the transfer of lower intestinal fluids and microbes from one individual to another — is sometimes used to treat inflammatory gut diseases, including ulcerative colitis and bacterial infections. Although a form of it was first recorded in 4th century China, it was introduced to western medicine in the 1950s. In the last two decades, it has steadily gained prominence.
A team of researchers led by the Bork group at EMBL Heidelberg, along with their collaborators in the Netherlands and Australia, has now used this unusual medical procedure to ask a fascinating question — what happens when two gut microbiomes mix together?
The answer could hold clues to better therapeutic strategies for gut disorders as well as a richer understanding of how microbial species behave and interact in complex natural ecosystems.
Transplanting microbes
Although clinical trials have demonstrated that FMTs can effectively treat certain gut disorders, their mode of action remains unclear. Some hypothesise the gut microbiomes of donors have beneficial properties that help return the recipient’s gut to a healthy state. However, this has never been systematically studied.
“The ‘super donor’ hypothesis is widely held among practitioners: it postulates that finding ‘good’ donors is essential to the clinical success of an FMT and that a good donor will work for many different patients,” said Sebastian Schmidt, one of the first authors of a new study published in Nature Medicine.
However, using clinical and metagenomics data from over 300 FMTs, the researchers discovered that it’s probably the recipient and not the donor that primarily determines the microbial mix resulting from this procedure. This builds upon a 2016 study from the Bork group that showed that microbial strains from a donor can coexist with those from a recipient with metabolic syndrome.

As a part of our immune defences, cytotoxic T cells — or killer T cells — seek out and destroy cells that are infected or cancerous. This process is essential for the body’s defence against diseases.
These specialised immune cells are armed with lytic granules containing two key components for immune attack: perforin (proteins that punch holes in the target cells) and granzymes (which gain access via these holes and ultimately kill disease-causing cells).
T cells snuggle up to targeted diseased cells and form an intimate junction between the two, called the ‘cytotoxic immunological synapse’.
A research team at UNSW Sydney’s EMBL Australia Node in Single Molecule Science in the School of Biomedical Sciences has found that mechanical forces generated by T cells influence how effectively perforin can punch through tumour cell membranes. In a paper published today in Developmental Cell, they describe the cell interactions and the integration of forces at both the front and rear of the cell.
The researchers detected physical forces within T cells that propel lytic granules toward the immunological synapse where their payloads are released. These forces also enable T cells to grab onto regions of the cancer cell membrane where the membranes of both immune and target cells are pulled and manipulated.
“It was very exciting to discover that, in addition to its mechanical tension and biochemical configuration, the shape of the target cell membrane plays an important role in T cell mediated cancer cell killing,” said Dr Daryan Kempe at UNSW Medicine & Health who co-led the research.